<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019cc527-3066-7ffb-9324-15e32595ee0e,g:55e32ec0-d65c-4e62-abcc-abc4e059e291-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.rigel.com/role/CONDENSEDSTATEMENTSOFOPERATIONS" xlink:type="simple" xlink:href="rigl-20260331.xsd#CONDENSEDSTATEMENTSOFOPERATIONS"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/CONDENSEDSTATEMENTSOFOPERATIONS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019cc527-3169-7ddb-a76c-6c685ce72d35" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:to="loc_us-gaap_StatementTable_019cc527-3169-7ddb-a76c-6c685ce72d35" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019cc527-3169-77b5-98a4-5803ff96eb24" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019cc527-3169-7ddb-a76c-6c685ce72d35" xlink:to="loc_srt_ProductOrServiceAxis_019cc527-3169-77b5-98a4-5803ff96eb24" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cc527-3169-77b5-98a4-5803ff96eb24_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019cc527-3169-77b5-98a4-5803ff96eb24" xlink:to="loc_srt_ProductsAndServicesDomain_019cc527-3169-77b5-98a4-5803ff96eb24_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cc527-3169-7acd-82eb-371baa73cbf2" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019cc527-3169-77b5-98a4-5803ff96eb24" xlink:to="loc_srt_ProductsAndServicesDomain_019cc527-3169-7acd-82eb-371baa73cbf2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_019cc527-3169-7aec-a74b-19c01e4ff622" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cc527-3169-7acd-82eb-371baa73cbf2" xlink:to="loc_us-gaap_ProductMember_019cc527-3169-7aec-a74b-19c01e4ff622" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ContractRevenuesFromCollaborationsMember_019cc527-3169-768b-a9cd-1d67318d8dd9" xlink:href="rigl-20260331.xsd#rigl_ContractRevenuesFromCollaborationsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cc527-3169-7acd-82eb-371baa73cbf2" xlink:to="loc_rigl_ContractRevenuesFromCollaborationsMember_019cc527-3169-768b-a9cd-1d67318d8dd9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesAbstract_019d1b00-d142-7b6e-ab27-14f27a698e9f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenuesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:to="loc_us-gaap_RevenuesAbstract_019d1b00-d142-7b6e-ab27-14f27a698e9f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019cc527-3169-728f-a03c-be8783ec82c2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesAbstract_019d1b00-d142-7b6e-ab27-14f27a698e9f" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019cc527-3169-728f-a03c-be8783ec82c2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3169-7021-a3f0-15e6593aa0da" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostsAndExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:to="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3169-7021-a3f0-15e6593aa0da" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_019cc527-3169-767e-8075-7504813687d4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3169-7021-a3f0-15e6593aa0da" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_019cc527-3169-767e-8075-7504813687d4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_019d1b09-9b96-7cc7-955c-4977111a2e59" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3169-7021-a3f0-15e6593aa0da" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_019d1b09-9b96-7cc7-955c-4977111a2e59" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_019cc527-3169-7250-bb4d-6feb9b888a55" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3169-7021-a3f0-15e6593aa0da" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_019cc527-3169-7250-bb4d-6feb9b888a55" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_019cc527-3169-7a2f-bd5a-3f6fb2dfee46" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostsAndExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3169-7021-a3f0-15e6593aa0da" xlink:to="loc_us-gaap_CostsAndExpenses_019cc527-3169-7a2f-bd5a-3f6fb2dfee46" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_019cc527-3169-7e8a-ba99-bbc75fd96be8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:to="loc_us-gaap_OperatingIncomeLoss_019cc527-3169-7e8a-ba99-bbc75fd96be8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentIncomeInterest_019cc527-3169-70d1-bcc6-c6ac4152b196" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentIncomeInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:to="loc_us-gaap_InvestmentIncomeInterest_019cc527-3169-70d1-bcc6-c6ac4152b196" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_019d1b0a-6662-7801-bded-411fcc961a08" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:to="loc_us-gaap_InterestExpenseNonoperating_019d1b0a-6662-7801-bded-411fcc961a08" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019cc527-3169-7a8b-b129-9f47041f047f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019cc527-3169-7a8b-b129-9f47041f047f" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_019cc527-3169-7063-b20c-9d94a6f2d9b3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_019cc527-3169-7063-b20c-9d94a6f2d9b3" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019cc527-3169-73f6-b556-0e2347936712" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:to="loc_us-gaap_NetIncomeLoss_019cc527-3169-73f6-b556-0e2347936712" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareAbstract_019cc527-3169-7667-88e0-edccb7fdf7af" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:to="loc_us-gaap_EarningsPerShareAbstract_019cc527-3169-7667-88e0-edccb7fdf7af" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_019cc527-3169-7a60-b6fb-99e157573caf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareAbstract_019cc527-3169-7667-88e0-edccb7fdf7af" xlink:to="loc_us-gaap_EarningsPerShareBasic_019cc527-3169-7a60-b6fb-99e157573caf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_019cc527-3169-7bda-99b7-28a7d008e778" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareAbstract_019cc527-3169-7667-88e0-edccb7fdf7af" xlink:to="loc_us-gaap_EarningsPerShareDiluted_019cc527-3169-7bda-99b7-28a7d008e778" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract_019cc527-3169-7cbe-b946-52d1b0e40b90" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7273-8889-b5bd5c497259" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract_019cc527-3169-7cbe-b946-52d1b0e40b90" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_019cc527-3169-7bbc-904f-cae438a97a44" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract_019cc527-3169-7cbe-b946-52d1b0e40b90" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_019cc527-3169-7bbc-904f-cae438a97a44" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019cc527-3169-763b-a51d-4c83abb96e76" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingAbstract_019cc527-3169-7cbe-b946-52d1b0e40b90" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019cc527-3169-763b-a51d-4c83abb96e76" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/CONDENSEDSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:type="simple" xlink:href="rigl-20260331.xsd#CONDENSEDSTATEMENTSOFSTOCKHOLDERSEQUITY"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/CONDENSEDSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019cc527-3169-7cd0-808a-daca036d6f3b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019cc527-3169-7ae1-8779-7514e70e7ad1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7cd0-808a-daca036d6f3b" xlink:to="loc_us-gaap_StatementTable_019cc527-3169-7ae1-8779-7514e70e7ad1" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_019cc527-3169-76cc-84a2-c719d65420bd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019cc527-3169-7ae1-8779-7514e70e7ad1" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_019cc527-3169-76cc-84a2-c719d65420bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019cc527-3169-76cc-84a2-c719d65420bd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019cc527-3169-76cc-84a2-c719d65420bd" xlink:to="loc_us-gaap_EquityComponentDomain_019cc527-3169-76cc-84a2-c719d65420bd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019cc527-3169-7d73-9721-696f8c8b39a8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019cc527-3169-76cc-84a2-c719d65420bd" xlink:to="loc_us-gaap_EquityComponentDomain_019cc527-3169-7d73-9721-696f8c8b39a8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_019cc527-3169-72f4-b953-4918c8a480be" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019cc527-3169-7d73-9721-696f8c8b39a8" xlink:to="loc_us-gaap_CommonStockMember_019cc527-3169-72f4-b953-4918c8a480be" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_019cc527-3169-7fe6-912b-20b2533208f9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019cc527-3169-7d73-9721-696f8c8b39a8" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_019cc527-3169-7fe6-912b-20b2533208f9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019cc527-3169-77cd-82d9-65d45b31fcb5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019cc527-3169-7d73-9721-696f8c8b39a8" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019cc527-3169-77cd-82d9-65d45b31fcb5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_019cc527-3169-77cd-be38-0cd386a2bc88" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019cc527-3169-7d73-9721-696f8c8b39a8" xlink:to="loc_us-gaap_RetainedEarningsMember_019cc527-3169-77cd-be38-0cd386a2bc88" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cc527-3169-7cd0-808a-daca036d6f3b" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_019cc527-3169-7caf-943d-c4c073b54418" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:to="loc_us-gaap_SharesIssued_019cc527-3169-7caf-943d-c4c073b54418" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019cc527-3169-7579-a53e-0d2daf16890e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:to="loc_us-gaap_StockholdersEquity_019cc527-3169-7579-a53e-0d2daf16890e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019d880d-dd31-70bd-b890-3666461ce056" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:to="loc_us-gaap_NetIncomeLoss_019d880d-dd31-70bd-b890-3666461ce056" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_019cc527-3169-78b6-80ed-5ca0f00ca076" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:to="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_019cc527-3169-78b6-80ed-5ca0f00ca076" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_019cc527-3169-7716-90d4-c8d315af8853" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_019cc527-3169-7716-90d4-c8d315af8853" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_019cc527-3169-7a0e-a551-ed5323cc4268" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_019cc527-3169-7a0e-a551-ed5323cc4268" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures_019cc527-3169-71aa-92ad-2da74db07476" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures_019cc527-3169-71aa-92ad-2da74db07476" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_019d1b2b-7824-7db1-a042-123bb84757ec" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:to="loc_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_019d1b2b-7824-7db1-a042-123bb84757ec" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_019d8816-f884-7fa1-b465-bbba0b3d9dd6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:to="loc_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_019d8816-f884-7fa1-b465-bbba0b3d9dd6" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_019cc527-3169-75b6-a655-774a6028fc30" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cc527-3169-7c74-8479-a58898a1e77a" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_019cc527-3169-75b6-a655-774a6028fc30" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_019cc527-3169-79f0-afa5-5bf0c658bd53" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharesIssued"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019cc527-3169-7892-ba83-53a5fa4b3444" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/NetIncomePerShareScheduleofAntidilutiveSecuritiesDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#NetIncomePerShareScheduleofAntidilutiveSecuritiesDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/NetIncomePerShareScheduleofAntidilutiveSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019cc527-3169-7d0c-b8d8-5c82a583fc8c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019cc527-3169-732f-ba1b-b21227125fe4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019cc527-3169-7d0c-b8d8-5c82a583fc8c" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019cc527-3169-732f-ba1b-b21227125fe4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019cc527-3169-75b1-86e6-9bfe7275e02f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019cc527-3169-732f-ba1b-b21227125fe4" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019cc527-3169-75b1-86e6-9bfe7275e02f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cc527-3169-75b1-86e6-9bfe7275e02f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019cc527-3169-75b1-86e6-9bfe7275e02f" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cc527-3169-75b1-86e6-9bfe7275e02f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cc527-3169-7573-a9bf-04b2dcc85c92" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019cc527-3169-75b1-86e6-9bfe7275e02f" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cc527-3169-7573-a9bf-04b2dcc85c92" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_019cc527-3169-7bc0-9454-be9971c00eb0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cc527-3169-7573-a9bf-04b2dcc85c92" xlink:to="loc_us-gaap_EmployeeStockOptionMember_019cc527-3169-7bc0-9454-be9971c00eb0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019cc527-3169-74bf-8474-791064e1e7fe" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cc527-3169-7573-a9bf-04b2dcc85c92" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019cc527-3169-74bf-8474-791064e1e7fe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_019cc527-3169-76d9-8327-65b7879210bb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cc527-3169-7573-a9bf-04b2dcc85c92" xlink:to="loc_us-gaap_EmployeeStockMember_019cc527-3169-76d9-8327-65b7879210bb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_019cc527-3169-7dd4-9ae5-6647fdeb96d0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019cc527-3169-7d0c-b8d8-5c82a583fc8c" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_019cc527-3169-7dd4-9ae5-6647fdeb96d0" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/RevenuesScheduleofRevenuesDisaggregatedbyCategoryDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#RevenuesScheduleofRevenuesDisaggregatedbyCategoryDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/RevenuesScheduleofRevenuesDisaggregatedbyCategoryDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_019cc527-3169-78e2-aded-2042b81a9c40" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_019cc527-3169-7cc1-80af-d091b8108e68" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cc527-3169-78e2-aded-2042b81a9c40" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_019cc527-3169-7cc1-80af-d091b8108e68" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019cc527-3169-7153-98ad-181351919d15" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019cc527-3169-7cc1-80af-d091b8108e68" xlink:to="loc_srt_ProductOrServiceAxis_019cc527-3169-7153-98ad-181351919d15" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cc527-3169-7153-98ad-181351919d15_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019cc527-3169-7153-98ad-181351919d15" xlink:to="loc_srt_ProductsAndServicesDomain_019cc527-3169-7153-98ad-181351919d15_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cc527-3169-7fdf-bb68-ce49f274a9aa" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019cc527-3169-7153-98ad-181351919d15" xlink:to="loc_srt_ProductsAndServicesDomain_019cc527-3169-7fdf-bb68-ce49f274a9aa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_019cc527-3169-722a-b4bd-82123e826051" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cc527-3169-7fdf-bb68-ce49f274a9aa" xlink:to="loc_us-gaap_ProductMember_019cc527-3169-722a-b4bd-82123e826051" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_GrossProductMember_019cc527-3169-7f01-93e5-f7f332859ed6" xlink:href="rigl-20260331.xsd#rigl_GrossProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_019cc527-3169-722a-b4bd-82123e826051" xlink:to="loc_rigl_GrossProductMember_019cc527-3169-7f01-93e5-f7f332859ed6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_DiscountsAndAllowancesMember_019cc527-3169-749f-95db-9f3a9447849f" xlink:href="rigl-20260331.xsd#rigl_DiscountsAndAllowancesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_019cc527-3169-722a-b4bd-82123e826051" xlink:to="loc_rigl_DiscountsAndAllowancesMember_019cc527-3169-749f-95db-9f3a9447849f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ContractRevenuesFromCollaborationsMember_019cc527-3169-77b0-be68-e8b27746be13" xlink:href="rigl-20260331.xsd#rigl_ContractRevenuesFromCollaborationsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cc527-3169-7fdf-bb68-ce49f274a9aa" xlink:to="loc_rigl_ContractRevenuesFromCollaborationsMember_019cc527-3169-77b0-be68-e8b27746be13" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_DevelopmentMilestonesMember_019cc527-3169-7bef-94c5-d871d6a9aeba" xlink:href="rigl-20260331.xsd#rigl_DevelopmentMilestonesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_ContractRevenuesFromCollaborationsMember_019cc527-3169-77b0-be68-e8b27746be13" xlink:to="loc_rigl_DevelopmentMilestonesMember_019cc527-3169-7bef-94c5-d871d6a9aeba" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_RoyaltyDeliveryOfDrugSuppliesAndOthersMember_019cc527-3169-7bff-80d3-2a482c121efa" xlink:href="rigl-20260331.xsd#rigl_RoyaltyDeliveryOfDrugSuppliesAndOthersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_ContractRevenuesFromCollaborationsMember_019cc527-3169-77b0-be68-e8b27746be13" xlink:to="loc_rigl_RoyaltyDeliveryOfDrugSuppliesAndOthersMember_019cc527-3169-7bff-80d3-2a482c121efa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019cc527-3169-75c9-b024-fa9dd893bfbb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cc527-3169-78e2-aded-2042b81a9c40" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019cc527-3169-75c9-b024-fa9dd893bfbb" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/RevenuesNarrativeDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#RevenuesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/RevenuesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_019d67d6-8f90-7594-a545-9e4c849d9d26" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ValuationAndQualifyingAccountsDisclosureLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_019d67d6-8f90-7de2-9d82-8b5f5fd4deb5" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ValuationAndQualifyingAccountsDisclosureTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_019d67d6-8f90-7594-a545-9e4c849d9d26" xlink:to="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_019d67d6-8f90-7de2-9d82-8b5f5fd4deb5" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_019d67d6-8f90-7c71-bf76-80d0175085e7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_019d67d6-8f90-7de2-9d82-8b5f5fd4deb5" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_019d67d6-8f90-7c71-bf76-80d0175085e7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDomain_019d67d6-8f90-7c71-bf76-80d0175085e7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_019d67d6-8f90-7c71-bf76-80d0175085e7" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDomain_019d67d6-8f90-7c71-bf76-80d0175085e7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDomain_019d67d6-8f90-74cc-aa81-0f0a41a611d8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_019d67d6-8f90-7c71-bf76-80d0175085e7" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDomain_019d67d6-8f90-74cc-aa81-0f0a41a611d8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllowanceForCreditLossMember_019d67d6-8f90-7805-b2cb-1440014de95e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AllowanceForCreditLossMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesDomain_019d67d6-8f90-74cc-aa81-0f0a41a611d8" xlink:to="loc_us-gaap_AllowanceForCreditLossMember_019d67d6-8f90-7805-b2cb-1440014de95e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense_019d67d6-8f90-7eb6-be0c-ef7ebf2b5e1f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_019d67d6-8f90-7594-a545-9e4c849d9d26" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense_019d67d6-8f90-7eb6-be0c-ef7ebf2b5e1f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDeductions_019d67d6-8f90-794a-b084-c88c8ac32aa9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesDeductions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_019d67d6-8f90-7594-a545-9e4c849d9d26" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDeductions_019d67d6-8f90-794a-b084-c88c8ac32aa9" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/RevenuesScheduleofProductRevenueAllowanceandReserveCategoriesDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#RevenuesScheduleofProductRevenueAllowanceandReserveCategoriesDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/RevenuesScheduleofProductRevenueAllowanceandReserveCategoriesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_019cc527-3169-7d6a-89bb-377a68616199" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ValuationAndQualifyingAccountsDisclosureLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_019cc527-3169-7a05-ae2c-cfa87933458c" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ValuationAndQualifyingAccountsDisclosureTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_019cc527-3169-7d6a-89bb-377a68616199" xlink:to="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_019cc527-3169-7a05-ae2c-cfa87933458c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_019cc527-3169-777f-9f39-6bc1f9245b4a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_019cc527-3169-7a05-ae2c-cfa87933458c" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_019cc527-3169-777f-9f39-6bc1f9245b4a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDomain_019cc527-3169-777f-9f39-6bc1f9245b4a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_019cc527-3169-777f-9f39-6bc1f9245b4a" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDomain_019cc527-3169-777f-9f39-6bc1f9245b4a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDomain_019cc527-3169-7df9-aec6-e47767f0b85d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_019cc527-3169-777f-9f39-6bc1f9245b4a" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDomain_019cc527-3169-7df9-aec6-e47767f0b85d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ChargebacksDiscountsAndFeesMember_019cc527-3169-7ce4-ae32-aed18dd11c6e" xlink:href="rigl-20260331.xsd#rigl_ChargebacksDiscountsAndFeesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesDomain_019cc527-3169-7df9-aec6-e47767f0b85d" xlink:to="loc_rigl_ChargebacksDiscountsAndFeesMember_019cc527-3169-7ce4-ae32-aed18dd11c6e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_GovernmentAndOtherRebatesMember_019cc527-3169-7bed-81f6-6066118f86a0" xlink:href="rigl-20260331.xsd#rigl_GovernmentAndOtherRebatesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesDomain_019cc527-3169-7df9-aec6-e47767f0b85d" xlink:to="loc_rigl_GovernmentAndOtherRebatesMember_019cc527-3169-7bed-81f6-6066118f86a0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SalesReturnsAndAllowancesMember_019cc527-3169-7ff3-b4b8-dbfcc7220429" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SalesReturnsAndAllowancesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesDomain_019cc527-3169-7df9-aec6-e47767f0b85d" xlink:to="loc_us-gaap_SalesReturnsAndAllowancesMember_019cc527-3169-7ff3-b4b8-dbfcc7220429" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MovementInValuationAllowancesAndReservesRollForward_019d67d8-5a80-7881-b590-899502659bb5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_MovementInValuationAllowancesAndReservesRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_019cc527-3169-7d6a-89bb-377a68616199" xlink:to="loc_us-gaap_MovementInValuationAllowancesAndReservesRollForward_019d67d8-5a80-7881-b590-899502659bb5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesBalance_019cc527-3169-7ada-b3bb-49dbe06ca9a7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesBalance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MovementInValuationAllowancesAndReservesRollForward_019d67d8-5a80-7881-b590-899502659bb5" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesBalance_019cc527-3169-7ada-b3bb-49dbe06ca9a7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense_019cc527-3169-7e5d-8a2d-b3a50ae5ab82" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MovementInValuationAllowancesAndReservesRollForward_019d67d8-5a80-7881-b590-899502659bb5" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense_019cc527-3169-7e5d-8a2d-b3a50ae5ab82" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesAdjustments_019cc527-3169-7c88-8633-d13acb793d02" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesAdjustments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MovementInValuationAllowancesAndReservesRollForward_019d67d8-5a80-7881-b590-899502659bb5" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesAdjustments_019cc527-3169-7c88-8633-d13acb793d02" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDeductions_019cc527-3169-7c81-8d6f-18420dad6397" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesDeductions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MovementInValuationAllowancesAndReservesRollForward_019d67d8-5a80-7881-b590-899502659bb5" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDeductions_019cc527-3169-7c81-8d6f-18420dad6397" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesBalance_019cc527-3169-7cb3-aaa1-8ba1c9bdcc67" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ValuationAllowancesAndReservesBalance"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/RevenuesScheduleofRevenuesFromProductSalesDisaggregatedbyCustomersDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#RevenuesScheduleofRevenuesFromProductSalesDisaggregatedbyCustomersDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/RevenuesScheduleofRevenuesFromProductSalesDisaggregatedbyCustomersDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_019cc527-3169-7be0-b994-f42eebe97c3c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_019cc527-3169-7ed2-b257-1750e8b57aa6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cc527-3169-7be0-b994-f42eebe97c3c" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_019cc527-3169-7ed2-b257-1750e8b57aa6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019cc527-3169-79b3-b3f9-a3586677df29" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019cc527-3169-7ed2-b257-1750e8b57aa6" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019cc527-3169-79b3-b3f9-a3586677df29" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cc527-3169-79b3-b3f9-a3586677df29_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019cc527-3169-79b3-b3f9-a3586677df29" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cc527-3169-79b3-b3f9-a3586677df29_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cc527-3169-757b-bb16-4c6163313edd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019cc527-3169-79b3-b3f9-a3586677df29" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cc527-3169-757b-bb16-4c6163313edd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SalesRevenueNetMember_019dd0e6-2282-7276-b9ab-4d6aef9a29b8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SalesRevenueNetMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cc527-3169-757b-bb16-4c6163313edd" xlink:to="loc_us-gaap_SalesRevenueNetMember_019dd0e6-2282-7276-b9ab-4d6aef9a29b8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_019cc527-3169-77ea-8e45-3d5292c114de" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019cc527-3169-7ed2-b257-1750e8b57aa6" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_019cc527-3169-77ea-8e45-3d5292c114de" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_019cc527-3169-77ea-8e45-3d5292c114de_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_019cc527-3169-77ea-8e45-3d5292c114de" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_019cc527-3169-77ea-8e45-3d5292c114de_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_019cc527-3169-720b-aa91-e512122a74d9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_019cc527-3169-77ea-8e45-3d5292c114de" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_019cc527-3169-720b-aa91-e512122a74d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerConcentrationRiskMember_019cc527-3169-74aa-b078-edbc7e7f13da" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CustomerConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_019cc527-3169-720b-aa91-e512122a74d9" xlink:to="loc_us-gaap_CustomerConcentrationRiskMember_019cc527-3169-74aa-b078-edbc7e7f13da" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_019cc527-3169-726e-bd88-05d2e9e05d17" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019cc527-3169-7ed2-b257-1750e8b57aa6" xlink:to="loc_srt_MajorCustomersAxis_019cc527-3169-726e-bd88-05d2e9e05d17" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_019cc527-3169-726e-bd88-05d2e9e05d17_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_019cc527-3169-726e-bd88-05d2e9e05d17" xlink:to="loc_srt_NameOfMajorCustomerDomain_019cc527-3169-726e-bd88-05d2e9e05d17_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_019cc527-3169-7218-ac8a-e5dd3e7e0eea" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_019cc527-3169-726e-bd88-05d2e9e05d17" xlink:to="loc_srt_NameOfMajorCustomerDomain_019cc527-3169-7218-ac8a-e5dd3e7e0eea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_MckessonSpecialtyCareDistributionCorporationMember_019cc527-3169-71ff-836d-8baeff2caaba" xlink:href="rigl-20260331.xsd#rigl_MckessonSpecialtyCareDistributionCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_019cc527-3169-7218-ac8a-e5dd3e7e0eea" xlink:to="loc_rigl_MckessonSpecialtyCareDistributionCorporationMember_019cc527-3169-71ff-836d-8baeff2caaba" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CencoraIncMember_019cc527-3169-7d3c-95a0-6d69cd2c7ddc" xlink:href="rigl-20260331.xsd#rigl_CencoraIncMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_019cc527-3169-7218-ac8a-e5dd3e7e0eea" xlink:to="loc_rigl_CencoraIncMember_019cc527-3169-7d3c-95a0-6d69cd2c7ddc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_OptimeCareIncMember_019cc527-3169-7dbd-a723-fae4d238468d" xlink:href="rigl-20260331.xsd#rigl_OptimeCareIncMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_019cc527-3169-7218-ac8a-e5dd3e7e0eea" xlink:to="loc_rigl_OptimeCareIncMember_019cc527-3169-7dbd-a723-fae4d238468d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CardinalHealthIncMember_019cc527-3169-7b6a-a12f-38b3fd051629" xlink:href="rigl-20260331.xsd#rigl_CardinalHealthIncMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_019cc527-3169-7218-ac8a-e5dd3e7e0eea" xlink:to="loc_rigl_CardinalHealthIncMember_019cc527-3169-7b6a-a12f-38b3fd051629" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_019cc527-3169-77d0-908c-6ff6c5d089e9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cc527-3169-7be0-b994-f42eebe97c3c" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_019cc527-3169-77d0-908c-6ff6c5d089e9" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/SponsoredResearchandLicenseAgreementsDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#SponsoredResearchandLicenseAgreementsDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/SponsoredResearchandLicenseAgreementsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_019cc527-3246-789e-a18a-82a324badf16" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_019cc527-3169-7917-a6cd-2504e027d49d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_019cc527-3246-789e-a18a-82a324badf16" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_019cc527-3169-7917-a6cd-2504e027d49d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_019cc527-3246-7019-9036-b21579cf8f6e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_019cc527-3169-7917-a6cd-2504e027d49d" xlink:to="loc_us-gaap_TypeOfArrangementAxis_019cc527-3246-7019-9036-b21579cf8f6e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019cc527-3246-7019-9036-b21579cf8f6e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019cc527-3246-7019-9036-b21579cf8f6e" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019cc527-3246-7019-9036-b21579cf8f6e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019cc527-3246-7a09-bc07-22ee8bb5259d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019cc527-3246-7019-9036-b21579cf8f6e" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019cc527-3246-7a09-bc07-22ee8bb5259d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementMember_019d1f04-cf3c-73a4-9b90-365e9ea6d193" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CollaborativeArrangementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019cc527-3246-7a09-bc07-22ee8bb5259d" xlink:to="loc_us-gaap_CollaborativeArrangementMember_019d1f04-cf3c-73a4-9b90-365e9ea6d193" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_StrategicCollaborationAgreementWithMdaccMember_019cc527-3246-70f7-bc7c-92aea4978501" xlink:href="rigl-20260331.xsd#rigl_StrategicCollaborationAgreementWithMdaccMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019cc527-3246-7a09-bc07-22ee8bb5259d" xlink:to="loc_rigl_StrategicCollaborationAgreementWithMdaccMember_019cc527-3246-70f7-bc7c-92aea4978501" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_StrategicCollaborationAgreementWithConnectMember_019cc527-3246-7f09-9dcb-c9afc2cde0fd" xlink:href="rigl-20260331.xsd#rigl_StrategicCollaborationAgreementWithConnectMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019cc527-3246-7a09-bc07-22ee8bb5259d" xlink:to="loc_rigl_StrategicCollaborationAgreementWithConnectMember_019cc527-3246-7f09-9dcb-c9afc2cde0fd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_AchievementOfMilestoneAxis_019cc527-3246-7d0d-b37d-27116da484a2" xlink:href="rigl-20260331.xsd#rigl_AchievementOfMilestoneAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_019cc527-3169-7917-a6cd-2504e027d49d" xlink:to="loc_rigl_AchievementOfMilestoneAxis_019cc527-3246-7d0d-b37d-27116da484a2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7d0d-b37d-27116da484a2_default" xlink:href="rigl-20260331.xsd#rigl_AchievementOfMilestoneDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_rigl_AchievementOfMilestoneAxis_019cc527-3246-7d0d-b37d-27116da484a2" xlink:to="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7d0d-b37d-27116da484a2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7d10-9e48-c7e28b144f74" xlink:href="rigl-20260331.xsd#rigl_AchievementOfMilestoneDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_rigl_AchievementOfMilestoneAxis_019cc527-3246-7d0d-b37d-27116da484a2" xlink:to="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7d10-9e48-c7e28b144f74" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_SpecifiedDevelopmentEventsMember_019cc527-3246-7c7b-b94d-3bf93e4df47a" xlink:href="rigl-20260331.xsd#rigl_SpecifiedDevelopmentEventsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7d10-9e48-c7e28b144f74" xlink:to="loc_rigl_SpecifiedDevelopmentEventsMember_019cc527-3246-7c7b-b94d-3bf93e4df47a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_SpecifiedProductLaunchEventsMember_019cc527-3246-7518-95d7-a9511af83fc2" xlink:href="rigl-20260331.xsd#rigl_SpecifiedProductLaunchEventsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7d10-9e48-c7e28b144f74" xlink:to="loc_rigl_SpecifiedProductLaunchEventsMember_019cc527-3246-7518-95d7-a9511af83fc2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_NonCentralNervousSystemSpecifiedDevelopmentAndRegulatoryMilestoneMember_019d1f06-3680-764a-82b9-461018cc0cc7" xlink:href="rigl-20260331.xsd#rigl_NonCentralNervousSystemSpecifiedDevelopmentAndRegulatoryMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7d10-9e48-c7e28b144f74" xlink:to="loc_rigl_NonCentralNervousSystemSpecifiedDevelopmentAndRegulatoryMilestoneMember_019d1f06-3680-764a-82b9-461018cc0cc7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ProductByProductSalesMilestoneMember_019d1f06-916e-732f-9e98-c1b6a9880f40" xlink:href="rigl-20260331.xsd#rigl_ProductByProductSalesMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7d10-9e48-c7e28b144f74" xlink:to="loc_rigl_ProductByProductSalesMilestoneMember_019d1f06-916e-732f-9e98-c1b6a9880f40" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CentralNervousSystemSpecifiedDevelopmentAndRegulatoryMilestoneMember_019d1f07-6c7b-7c3d-9f16-64221e77625c" xlink:href="rigl-20260331.xsd#rigl_CentralNervousSystemSpecifiedDevelopmentAndRegulatoryMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7d10-9e48-c7e28b144f74" xlink:to="loc_rigl_CentralNervousSystemSpecifiedDevelopmentAndRegulatoryMilestoneMember_019d1f07-6c7b-7c3d-9f16-64221e77625c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CentralNervousSystemProductByProductSalesMilestoneMember_019d1f07-ca30-7316-b162-e776ff614c0d" xlink:href="rigl-20260331.xsd#rigl_CentralNervousSystemProductByProductSalesMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7d10-9e48-c7e28b144f74" xlink:to="loc_rigl_CentralNervousSystemProductByProductSalesMilestoneMember_019d1f07-ca30-7316-b162-e776ff614c0d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_OneTimeDeliveryOfDrugSupplyForCommercializationMember_019cc527-3246-7ad7-be8c-45e72117680b" xlink:href="rigl-20260331.xsd#rigl_OneTimeDeliveryOfDrugSupplyForCommercializationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7d10-9e48-c7e28b144f74" xlink:to="loc_rigl_OneTimeDeliveryOfDrugSupplyForCommercializationMember_019cc527-3246-7ad7-be8c-45e72117680b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_019d1f14-a71f-7d99-a59c-7faa1a5c50a0" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_019cc527-3169-7917-a6cd-2504e027d49d" xlink:to="loc_srt_CounterpartyNameAxis_019d1f14-a71f-7d99-a59c-7faa1a5c50a0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d1f14-a71f-7d99-a59c-7faa1a5c50a0_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_019d1f14-a71f-7d99-a59c-7faa1a5c50a0" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d1f14-a71f-7d99-a59c-7faa1a5c50a0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d1f14-a71f-7daf-86ee-80046f6ef3df" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_019d1f14-a71f-7d99-a59c-7faa1a5c50a0" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d1f14-a71f-7daf-86ee-80046f6ef3df" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_GrifolsS.a.Member_019d1f1d-5a58-797d-90c4-09d11e286155" xlink:href="rigl-20260331.xsd#rigl_GrifolsS.a.Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d1f14-a71f-7daf-86ee-80046f6ef3df" xlink:to="loc_rigl_GrifolsS.a.Member_019d1f1d-5a58-797d-90c4-09d11e286155" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_KisseiPharmaceuticalCo.Ltd.Member_019d1f14-d4e4-7db8-bf2f-e3ecb9103be4" xlink:href="rigl-20260331.xsd#rigl_KisseiPharmaceuticalCo.Ltd.Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d1f14-a71f-7daf-86ee-80046f6ef3df" xlink:to="loc_rigl_KisseiPharmaceuticalCo.Ltd.Member_019d1f14-d4e4-7db8-bf2f-e3ecb9103be4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_MedisonPharmaLtd.Member_019d1f16-8118-76e3-baf2-cc28e3a26328" xlink:href="rigl-20260331.xsd#rigl_MedisonPharmaLtd.Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d1f14-a71f-7daf-86ee-80046f6ef3df" xlink:to="loc_rigl_MedisonPharmaLtd.Member_019d1f16-8118-76e3-baf2-cc28e3a26328" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019cc527-3246-71f6-99c5-13cb4f455bef" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_019cc527-3169-7917-a6cd-2504e027d49d" xlink:to="loc_srt_ProductOrServiceAxis_019cc527-3246-71f6-99c5-13cb4f455bef" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cc527-3246-71f6-99c5-13cb4f455bef_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019cc527-3246-71f6-99c5-13cb4f455bef" xlink:to="loc_srt_ProductsAndServicesDomain_019cc527-3246-71f6-99c5-13cb4f455bef_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cc527-3246-7597-ac52-24c9af62d3ca" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019cc527-3246-71f6-99c5-13cb4f455bef" xlink:to="loc_srt_ProductsAndServicesDomain_019cc527-3246-7597-ac52-24c9af62d3ca" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_OcadusertibMember_019cc527-3246-71fc-adf2-004b6c348456" xlink:href="rigl-20260331.xsd#rigl_OcadusertibMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cc527-3246-7597-ac52-24c9af62d3ca" xlink:to="loc_rigl_OcadusertibMember_019cc527-3246-71fc-adf2-004b6c348456" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RoyaltyMember_019cc527-3246-75c4-ac52-508688b5c462" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RoyaltyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cc527-3246-7597-ac52-24c9af62d3ca" xlink:to="loc_us-gaap_RoyaltyMember_019cc527-3246-75c4-ac52-508688b5c462" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_FostamatinibMember_019cc527-3246-70ee-ba94-c7586c2b0861" xlink:href="rigl-20260331.xsd#rigl_FostamatinibMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cc527-3246-7597-ac52-24c9af62d3ca" xlink:to="loc_rigl_FostamatinibMember_019cc527-3246-70ee-ba94-c7586c2b0861" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_RezlidhiaMember_019cc527-3246-7549-a8c6-f3540901086f" xlink:href="rigl-20260331.xsd#rigl_RezlidhiaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cc527-3246-7597-ac52-24c9af62d3ca" xlink:to="loc_rigl_RezlidhiaMember_019cc527-3246-7549-a8c6-f3540901086f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ContingentPaymentsUnderAgreement_019cc527-3246-7a03-85d6-6c9a964af0fb" xlink:href="rigl-20260331.xsd#rigl_ContingentPaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_019cc527-3246-789e-a18a-82a324badf16" xlink:to="loc_rigl_ContingentPaymentsUnderAgreement_019cc527-3246-7a03-85d6-6c9a964af0fb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CollaborativeArrangementUpfrontFeeReceived_019cc527-3246-7679-9dda-85c3676e538b" xlink:href="rigl-20260331.xsd#rigl_CollaborativeArrangementUpfrontFeeReceived"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_019cc527-3246-789e-a18a-82a324badf16" xlink:to="loc_rigl_CollaborativeArrangementUpfrontFeeReceived_019cc527-3246-7679-9dda-85c3676e538b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_DevelopmentCostsCostSharingArrangementPercentage_019cc527-3246-776d-a6cf-60ce9445d4a2" xlink:href="rigl-20260331.xsd#rigl_DevelopmentCostsCostSharingArrangementPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_019cc527-3246-789e-a18a-82a324badf16" xlink:to="loc_rigl_DevelopmentCostsCostSharingArrangementPercentage_019cc527-3246-776d-a6cf-60ce9445d4a2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CollaborativeArrangementRevenueRecognized_019cc527-3246-7f51-9c4d-903c9b3b405e" xlink:href="rigl-20260331.xsd#rigl_CollaborativeArrangementRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_019cc527-3246-789e-a18a-82a324badf16" xlink:to="loc_rigl_CollaborativeArrangementRevenueRecognized_019cc527-3246-7f51-9c4d-903c9b3b405e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_019d1f0b-7ef1-72aa-ad23-b35ab1f75ec3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_019cc527-3246-789e-a18a-82a324badf16" xlink:to="loc_us-gaap_ContractWithCustomerLiability_019d1f0b-7ef1-72aa-ad23-b35ab1f75ec3" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019d1f14-2513-7da4-ad1c-a0f02d9fe8ed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_019cc527-3246-789e-a18a-82a324badf16" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019d1f14-2513-7da4-ad1c-a0f02d9fe8ed" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_DueToCollaborationPartner_019cc527-3246-7681-9636-28377f3e6d53" xlink:href="rigl-20260331.xsd#rigl_DueToCollaborationPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_019cc527-3246-789e-a18a-82a324badf16" xlink:to="loc_rigl_DueToCollaborationPartner_019cc527-3246-7681-9636-28377f3e6d53" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CollaborationTerm_019cc527-3246-7517-87a9-16ab98b75932" xlink:href="rigl-20260331.xsd#rigl_CollaborationTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_019cc527-3246-789e-a18a-82a324badf16" xlink:to="loc_rigl_CollaborationTerm_019cc527-3246-7517-87a9-16ab98b75932" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_PaymentOfCostShareToCollaborationPartner_019cc527-3246-70a8-8563-9c9e3c3e5df4" xlink:href="rigl-20260331.xsd#rigl_PaymentOfCostShareToCollaborationPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_019cc527-3246-789e-a18a-82a324badf16" xlink:to="loc_rigl_PaymentOfCostShareToCollaborationPartner_019cc527-3246-70a8-8563-9c9e3c3e5df4" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/InlicensingandAcquisitionNarrativeDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#InlicensingandAcquisitionNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/InlicensingandAcquisitionNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionTable_019cc527-3246-7c1d-ba3f-2c2a62e62918" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_us-gaap_AssetAcquisitionTable_019cc527-3246-7c1d-ba3f-2c2a62e62918" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionAxis_019cc527-3246-7db9-a54e-0ec1e9f54555" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_019cc527-3246-7c1d-ba3f-2c2a62e62918" xlink:to="loc_us-gaap_AssetAcquisitionAxis_019cc527-3246-7db9-a54e-0ec1e9f54555" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_019cc527-3246-7db9-a54e-0ec1e9f54555_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetAcquisitionAxis_019cc527-3246-7db9-a54e-0ec1e9f54555" xlink:to="loc_us-gaap_AssetAcquisitionDomain_019cc527-3246-7db9-a54e-0ec1e9f54555_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_019cc527-3246-7939-9a0e-3b879dcb7083" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetAcquisitionAxis_019cc527-3246-7db9-a54e-0ec1e9f54555" xlink:to="loc_us-gaap_AssetAcquisitionDomain_019cc527-3246-7939-9a0e-3b879dcb7083" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_BlueprintMedicinesCorporationMember_019cc527-3246-747b-9c6e-14f268375ec6" xlink:href="rigl-20260331.xsd#rigl_BlueprintMedicinesCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionDomain_019cc527-3246-7939-9a0e-3b879dcb7083" xlink:to="loc_rigl_BlueprintMedicinesCorporationMember_019cc527-3246-747b-9c6e-14f268375ec6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019cc527-3246-7da6-a34d-16c2f3b3d0a1" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_019cc527-3246-7c1d-ba3f-2c2a62e62918" xlink:to="loc_srt_ProductOrServiceAxis_019cc527-3246-7da6-a34d-16c2f3b3d0a1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cc527-3246-7da6-a34d-16c2f3b3d0a1_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019cc527-3246-7da6-a34d-16c2f3b3d0a1" xlink:to="loc_srt_ProductsAndServicesDomain_019cc527-3246-7da6-a34d-16c2f3b3d0a1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cc527-3246-72d6-ad2e-2bcc8b22f55c" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019cc527-3246-7da6-a34d-16c2f3b3d0a1" xlink:to="loc_srt_ProductsAndServicesDomain_019cc527-3246-72d6-ad2e-2bcc8b22f55c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_GavretoMember_019cc527-3246-7a33-92e3-47752a41a875" xlink:href="rigl-20260331.xsd#rigl_GavretoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cc527-3246-72d6-ad2e-2bcc8b22f55c" xlink:to="loc_rigl_GavretoMember_019cc527-3246-7a33-92e3-47752a41a875" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_RezlidhiaMember_019cc527-3246-72a7-98f8-5c66efa4a9e1" xlink:href="rigl-20260331.xsd#rigl_RezlidhiaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cc527-3246-72d6-ad2e-2bcc8b22f55c" xlink:to="loc_rigl_RezlidhiaMember_019cc527-3246-72a7-98f8-5c66efa4a9e1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LegalEntityAxis_019cc527-3246-757f-b7c4-939fd9147947" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_LegalEntityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_019cc527-3246-7c1d-ba3f-2c2a62e62918" xlink:to="loc_dei_LegalEntityAxis_019cc527-3246-757f-b7c4-939fd9147947" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_019cc527-3246-757f-b7c4-939fd9147947_default" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dei_LegalEntityAxis_019cc527-3246-757f-b7c4-939fd9147947" xlink:to="loc_dei_EntityDomain_019cc527-3246-757f-b7c4-939fd9147947_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_019cc527-3246-7a38-bc81-9200c38a79c8" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dei_LegalEntityAxis_019cc527-3246-757f-b7c4-939fd9147947" xlink:to="loc_dei_EntityDomain_019cc527-3246-7a38-bc81-9200c38a79c8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_FormaTherapeuticsHoldingsIncMember_019cc527-3246-70fc-a2a5-a8b39d25d1c5" xlink:href="rigl-20260331.xsd#rigl_FormaTherapeuticsHoldingsIncMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_019cc527-3246-7a38-bc81-9200c38a79c8" xlink:to="loc_rigl_FormaTherapeuticsHoldingsIncMember_019cc527-3246-70fc-a2a5-a8b39d25d1c5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_AchievementOfMilestoneAxis_019cc527-3246-7753-9647-b3fb6a854a3b" xlink:href="rigl-20260331.xsd#rigl_AchievementOfMilestoneAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_019cc527-3246-7c1d-ba3f-2c2a62e62918" xlink:to="loc_rigl_AchievementOfMilestoneAxis_019cc527-3246-7753-9647-b3fb6a854a3b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7753-9647-b3fb6a854a3b_default" xlink:href="rigl-20260331.xsd#rigl_AchievementOfMilestoneDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_rigl_AchievementOfMilestoneAxis_019cc527-3246-7753-9647-b3fb6a854a3b" xlink:to="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7753-9647-b3fb6a854a3b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7a53-9c89-8a87330c4e13" xlink:href="rigl-20260331.xsd#rigl_AchievementOfMilestoneDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_rigl_AchievementOfMilestoneAxis_019cc527-3246-7753-9647-b3fb6a854a3b" xlink:to="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7a53-9c89-8a87330c4e13" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_FirstCommercialSaleMember_019cc527-3246-7617-b9dd-0c08a418ce31" xlink:href="rigl-20260331.xsd#rigl_FirstCommercialSaleMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7a53-9c89-8a87330c4e13" xlink:to="loc_rigl_FirstCommercialSaleMember_019cc527-3246-7617-b9dd-0c08a418ce31" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_FirstAnniversaryOfClosingDateMember_019cc527-3246-7ad2-8b8c-4195275a8351" xlink:href="rigl-20260331.xsd#rigl_FirstAnniversaryOfClosingDateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7a53-9c89-8a87330c4e13" xlink:to="loc_rigl_FirstAnniversaryOfClosingDateMember_019cc527-3246-7ad2-8b8c-4195275a8351" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_SpecifiedCommercialMilestonesMember_019cc527-3246-7553-92ef-d63b6598c2b8" xlink:href="rigl-20260331.xsd#rigl_SpecifiedCommercialMilestonesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7a53-9c89-8a87330c4e13" xlink:to="loc_rigl_SpecifiedCommercialMilestonesMember_019cc527-3246-7553-92ef-d63b6598c2b8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_RegulatoryMilestonesMember_019cc527-3246-7a5c-a46b-1bcc8d489bb3" xlink:href="rigl-20260331.xsd#rigl_RegulatoryMilestonesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7a53-9c89-8a87330c4e13" xlink:to="loc_rigl_RegulatoryMilestonesMember_019cc527-3246-7a5c-a46b-1bcc8d489bb3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_DevelopmentAndRegulatoryMilestonesMember_019cc527-3246-7e8b-baa3-37c3ec66963a" xlink:href="rigl-20260331.xsd#rigl_DevelopmentAndRegulatoryMilestonesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7a53-9c89-8a87330c4e13" xlink:to="loc_rigl_DevelopmentAndRegulatoryMilestonesMember_019cc527-3246-7e8b-baa3-37c3ec66963a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_AchievementOfCertainNearTermRegulatoryMilestoneMember_019cc527-3246-7c30-a2b0-2eb743bf6042" xlink:href="rigl-20260331.xsd#rigl_AchievementOfCertainNearTermRegulatoryMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7a53-9c89-8a87330c4e13" xlink:to="loc_rigl_AchievementOfCertainNearTermRegulatoryMilestoneMember_019cc527-3246-7c30-a2b0-2eb743bf6042" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_FDAApprovalAndFirstCommercialSaleOfProductMember_019cc527-3246-700b-b717-df1658dbbe3e" xlink:href="rigl-20260331.xsd#rigl_FDAApprovalAndFirstCommercialSaleOfProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_AchievementOfMilestoneDomain_019cc527-3246-7a53-9c89-8a87330c4e13" xlink:to="loc_rigl_FDAApprovalAndFirstCommercialSaleOfProductMember_019cc527-3246-700b-b717-df1658dbbe3e" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_019cc527-3246-74a2-8d9a-655df73d909a" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_019cc527-3246-7c1d-ba3f-2c2a62e62918" xlink:to="loc_srt_RangeAxis_019cc527-3246-74a2-8d9a-655df73d909a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019cc527-3246-74a2-8d9a-655df73d909a_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_019cc527-3246-74a2-8d9a-655df73d909a" xlink:to="loc_srt_RangeMember_019cc527-3246-74a2-8d9a-655df73d909a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019cc527-3246-7985-bde9-8c5924f7499b" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_019cc527-3246-74a2-8d9a-655df73d909a" xlink:to="loc_srt_RangeMember_019cc527-3246-7985-bde9-8c5924f7499b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_019cc527-3246-7440-bba9-910118f98fad" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019cc527-3246-7985-bde9-8c5924f7499b" xlink:to="loc_srt_MinimumMember_019cc527-3246-7440-bba9-910118f98fad" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_019cc527-3246-78d3-af52-7727878f203e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019cc527-3246-7985-bde9-8c5924f7499b" xlink:to="loc_srt_MaximumMember_019cc527-3246-78d3-af52-7727878f203e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionPriceOfAcquisitionExpected_019cc527-3246-7340-8dfe-cc4e2a5b5169" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionPriceOfAcquisitionExpected"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_us-gaap_AssetAcquisitionPriceOfAcquisitionExpected_019cc527-3246-7340-8dfe-cc4e2a5b5169" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_PotentialMilestonePaymentObligations_019cc527-3246-7c9b-bc25-2fb65b1c9607" xlink:href="rigl-20260331.xsd#rigl_PotentialMilestonePaymentObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_rigl_PotentialMilestonePaymentObligations_019cc527-3246-7c9b-bc25-2fb65b1c9607" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_PotentialTieredRoyaltyPercentage_019cc527-3246-7373-9019-bde8fa1bc8ca" xlink:href="rigl-20260331.xsd#rigl_PotentialTieredRoyaltyPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_rigl_PotentialTieredRoyaltyPercentage_019cc527-3246-7373-9019-bde8fa1bc8ca" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionConsiderationTransferred_019cc527-3246-794d-8901-f83f30a0adca" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionConsiderationTransferred"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_us-gaap_AssetAcquisitionConsiderationTransferred_019cc527-3246-794d-8901-f83f30a0adca" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireProductiveAssets_019cc527-3246-7ff2-b30d-ee46bc78a8e1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsToAcquireProductiveAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_us-gaap_PaymentsToAcquireProductiveAssets_019cc527-3246-7ff2-b30d-ee46bc78a8e1" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionConsiderationTransferredTransactionCost_019cc527-3246-71f3-88ea-b68ebb935303" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionConsiderationTransferredTransactionCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_us-gaap_AssetAcquisitionConsiderationTransferredTransactionCost_019cc527-3246-71f3-88ea-b68ebb935303" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionContingentConsiderationLiabilityCurrent_019cc527-3246-7824-baae-39016ee2e3ec" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetAcquisitionContingentConsiderationLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_us-gaap_AssetAcquisitionContingentConsiderationLiabilityCurrent_019cc527-3246-7824-baae-39016ee2e3ec" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife_019cc527-3246-78e1-8dc9-c333031b20ce" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife_019cc527-3246-78e1-8dc9-c333031b20ce" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CollaborativeArrangementUpfrontPayment_019cc527-3246-75d2-8da2-8ea3bfbb20dd" xlink:href="rigl-20260331.xsd#rigl_CollaborativeArrangementUpfrontPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_rigl_CollaborativeArrangementUpfrontPayment_019cc527-3246-75d2-8da2-8ea3bfbb20dd" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CollaborativeArrangementPotentialPayments_019cc527-3246-7d5d-aed6-5bd3dc6ea8d7" xlink:href="rigl-20260331.xsd#rigl_CollaborativeArrangementPotentialPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_rigl_CollaborativeArrangementPotentialPayments_019cc527-3246-7d5d-aed6-5bd3dc6ea8d7" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost_019cc527-3246-7270-8dbe-6b03d9cd0fc4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost_019cc527-3246-7270-8dbe-6b03d9cd0fc4" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_019d1f38-1371-71fe-a62a-32a427e5ede4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_019cc527-3246-74af-b2f9-cc8e15fc38b5" xlink:to="loc_us-gaap_AccountsPayableCurrent_019d1f38-1371-71fe-a62a-32a427e5ede4" xlink:type="arc" order="11"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/StockBasedCompensationScheduleofStockBasedCompensationDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#StockBasedCompensationScheduleofStockBasedCompensationDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/StockBasedCompensationScheduleofStockBasedCompensationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019cc527-3246-7ee3-a495-badb2ec7ac4a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cc527-3246-7f3c-b7f2-f6b6367f5001" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019cc527-3246-7ee3-a495-badb2ec7ac4a" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cc527-3246-7f3c-b7f2-f6b6367f5001" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_019cc527-3246-7253-983a-51fa574d3932" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cc527-3246-7f3c-b7f2-f6b6367f5001" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_019cc527-3246-7253-983a-51fa574d3932" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_019cc527-3246-7253-983a-51fa574d3932_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_019cc527-3246-7253-983a-51fa574d3932" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_019cc527-3246-7253-983a-51fa574d3932_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_019cc527-3246-74e2-9bf4-6f6b4c8668d8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_019cc527-3246-7253-983a-51fa574d3932" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_019cc527-3246-74e2-9bf4-6f6b4c8668d8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_019cc527-3246-7d2d-9d0a-a050d9c6b222" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_019cc527-3246-74e2-9bf4-6f6b4c8668d8" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_019cc527-3246-7d2d-9d0a-a050d9c6b222" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_019cc527-3246-770c-abf2-2a9a9c44e1d6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_019cc527-3246-74e2-9bf4-6f6b4c8668d8" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_019cc527-3246-770c-abf2-2a9a9c44e1d6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_019cc527-3246-73b1-a680-f2babb9d4391" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019cc527-3246-7ee3-a495-badb2ec7ac4a" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_019cc527-3246-73b1-a680-f2babb9d4391" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/StockBasedCompensationNarrativeDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#StockBasedCompensationNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/StockBasedCompensationNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019d1f46-ab20-7020-80fa-8b4c785d2c7c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019d1f46-ab20-7020-80fa-8b4c785d2c7c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019d1f46-ab20-7218-b899-0f55650c2d57" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019d1f46-ab20-7020-80fa-8b4c785d2c7c" xlink:to="loc_us-gaap_AwardTypeAxis_019d1f46-ab20-7218-b899-0f55650c2d57" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d1f46-ab20-7218-b899-0f55650c2d57_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019d1f46-ab20-7218-b899-0f55650c2d57" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d1f46-ab20-7218-b899-0f55650c2d57_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d1f46-ab20-7aa4-b40d-c9316e0cc3ed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019d1f46-ab20-7218-b899-0f55650c2d57" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d1f46-ab20-7aa4-b40d-c9316e0cc3ed" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ShareBasedCompensationOptionsAndRsusMember_019d1f47-e698-79fe-81f9-2d8bc8ac3962" xlink:href="rigl-20260331.xsd#rigl_ShareBasedCompensationOptionsAndRsusMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d1f46-ab20-7aa4-b40d-c9316e0cc3ed" xlink:to="loc_rigl_ShareBasedCompensationOptionsAndRsusMember_019d1f47-e698-79fe-81f9-2d8bc8ac3962" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_019d1f46-ab20-7b11-9693-691e86e80ec9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_ShareBasedCompensationOptionsAndRsusMember_019d1f47-e698-79fe-81f9-2d8bc8ac3962" xlink:to="loc_us-gaap_EmployeeStockOptionMember_019d1f46-ab20-7b11-9693-691e86e80ec9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019d1f47-e698-7378-87ac-f84434841184" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_ShareBasedCompensationOptionsAndRsusMember_019d1f47-e698-79fe-81f9-2d8bc8ac3962" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019d1f47-e698-7378-87ac-f84434841184" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_019d1f47-e698-7da7-a8a7-9891f8d7d526" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d1f46-ab20-7aa4-b40d-c9316e0cc3ed" xlink:to="loc_us-gaap_EmployeeStockMember_019d1f47-e698-7da7-a8a7-9891f8d7d526" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VestingAxis_019d1f46-ab20-7b4b-83f8-d6e2525e5674" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VestingAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019d1f46-ab20-7020-80fa-8b4c785d2c7c" xlink:to="loc_us-gaap_VestingAxis_019d1f46-ab20-7b4b-83f8-d6e2525e5674" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VestingDomain_019d1f46-ab20-7b4b-83f8-d6e2525e5674_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VestingDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_VestingAxis_019d1f46-ab20-7b4b-83f8-d6e2525e5674" xlink:to="loc_us-gaap_VestingDomain_019d1f46-ab20-7b4b-83f8-d6e2525e5674_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VestingDomain_019d1f46-ab20-7ae1-b233-629fd49b31ed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VestingDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_VestingAxis_019d1f46-ab20-7b4b-83f8-d6e2525e5674" xlink:to="loc_us-gaap_VestingDomain_019d1f46-ab20-7ae1-b233-629fd49b31ed" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationAwardTrancheOneMember_019d1f46-ab20-7b4c-bccf-c83b54859bfb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationAwardTrancheOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VestingDomain_019d1f46-ab20-7ae1-b233-629fd49b31ed" xlink:to="loc_us-gaap_ShareBasedCompensationAwardTrancheOneMember_019d1f46-ab20-7b4c-bccf-c83b54859bfb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_019d1f46-ab20-7ed0-b90d-a29a3ad46b51" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_019d1f46-ab20-7ed0-b90d-a29a3ad46b51" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019d1f46-ab20-7cae-b3d4-23ef18239488" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019d1f46-ab20-7cae-b3d4-23ef18239488" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019d1f47-e698-7766-97a5-43c5e29f838e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019d1f47-e698-7766-97a5-43c5e29f838e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019d1f47-e698-77da-87f7-4f210ee0051e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019d1f47-e698-77da-87f7-4f210ee0051e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_019d1f46-ab20-7843-8bff-3c6a8e9274c9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_019d1f46-ab20-7843-8bff-3c6a8e9274c9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019d1f46-ab20-7fe1-a3ae-276c09763f6f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019d1f46-ab20-7fe1-a3ae-276c09763f6f" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019d1f47-e698-72c0-ba24-e794e97ab896" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019d1f47-e698-72c0-ba24-e794e97ab896" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_019d1f68-eeca-7514-86f7-3b374618803c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_019d1f68-eeca-7514-86f7-3b374618803c" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_019d8b52-470c-73c6-b7e2-804b784f03a5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_019d8b52-470c-73c6-b7e2-804b784f03a5" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_019d1f46-ab20-71c6-bb94-3c91e73876e8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_019d1f46-ab20-71c6-bb94-3c91e73876e8" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019d1f47-e698-784d-811b-755eed6f6d88" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019d1f47-e698-784d-811b-755eed6f6d88" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_019d1f46-ab20-799b-9dff-67312d4b36a8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_019d1f46-ab20-799b-9dff-67312d4b36a8" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019d1f47-e698-7206-9195-7b84e4b40ca4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019d1f47-e698-7206-9195-7b84e4b40ca4" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_019d1f47-e698-7cb3-a780-7a4142a40483" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_019d1f47-e698-7cb3-a780-7a4142a40483" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ShareBasedCompensationArrangementByShareBasedPaymentAwardConsecutiveOfferingPeriod_019d1f6c-24f8-76bd-9aa3-9868d51182cf" xlink:href="rigl-20260331.xsd#rigl_ShareBasedCompensationArrangementByShareBasedPaymentAwardConsecutiveOfferingPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_rigl_ShareBasedCompensationArrangementByShareBasedPaymentAwardConsecutiveOfferingPeriod_019d1f6c-24f8-76bd-9aa3-9868d51182cf" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_019d1f47-e698-78b1-aaab-2e76a9017ac9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_019d1f47-e698-78b1-aaab-2e76a9017ac9" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_019d1f47-e698-72d1-bff8-70887760b33f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019d1f46-ab20-78a4-a8a3-1cb776be2176" xlink:to="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_019d1f47-e698-72d1-bff8-70887760b33f" xlink:type="arc" order="16"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/StockBasedCompensationScheduleofWeightedAverageAssumptionsRelatingtoOptionsGrantedDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#StockBasedCompensationScheduleofWeightedAverageAssumptionsRelatingtoOptionsGrantedDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/StockBasedCompensationScheduleofWeightedAverageAssumptionsRelatingtoOptionsGrantedDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019cc527-3246-7899-bef1-da32f7c7bebb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019cc527-3246-7f12-9653-1fabcaaaacae" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019cc527-3246-7899-bef1-da32f7c7bebb" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019cc527-3246-7f12-9653-1fabcaaaacae" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019cc527-3246-7a38-9233-6977868e704f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019cc527-3246-7f12-9653-1fabcaaaacae" xlink:to="loc_us-gaap_AwardTypeAxis_019cc527-3246-7a38-9233-6977868e704f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019cc527-3246-7a38-9233-6977868e704f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019cc527-3246-7a38-9233-6977868e704f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019cc527-3246-7a38-9233-6977868e704f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019cc527-3246-76a4-bca1-f25a02cc267f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019cc527-3246-7a38-9233-6977868e704f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019cc527-3246-76a4-bca1-f25a02cc267f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_019cc527-3246-7fd9-9709-942a78fb65fb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019cc527-3246-76a4-bca1-f25a02cc267f" xlink:to="loc_us-gaap_EmployeeStockOptionMember_019cc527-3246-7fd9-9709-942a78fb65fb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_019cc527-3246-7ee0-bccc-79f1f677100d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019cc527-3246-7899-bef1-da32f7c7bebb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_019cc527-3246-7ee0-bccc-79f1f677100d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_019cc527-3246-7188-997e-7785ba2e49a2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_019cc527-3246-7ee0-bccc-79f1f677100d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_019cc527-3246-7188-997e-7785ba2e49a2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_019cc527-3246-7daf-b392-14ca26ce51f7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_019cc527-3246-7ee0-bccc-79f1f677100d" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_019cc527-3246-7daf-b392-14ca26ce51f7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_019cc527-3246-7c1e-9af3-c5f5c059606f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_019cc527-3246-7ee0-bccc-79f1f677100d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_019cc527-3246-7c1e-9af3-c5f5c059606f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_019cc527-3246-76bb-bfeb-7c14ea704795" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_019cc527-3246-7ee0-bccc-79f1f677100d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_019cc527-3246-76bb-bfeb-7c14ea704795" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/CashCashEquivalentsRestrictedCashandShortTermInvestmentsScheduleofCashCashEquivalentsandShortTermInvestmentsDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#CashCashEquivalentsRestrictedCashandShortTermInvestmentsScheduleofCashCashEquivalentsandShortTermInvestmentsDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/CashCashEquivalentsRestrictedCashandShortTermInvestmentsScheduleofCashCashEquivalentsandShortTermInvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019cc527-3246-75d3-b08b-16302d53cfcb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable_019cc527-3246-7c4a-906d-46cc8929fc60" xlink:href="rigl-20260331.xsd#rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019cc527-3246-75d3-b08b-16302d53cfcb" xlink:to="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable_019cc527-3246-7c4a-906d-46cc8929fc60" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAxis_019cc527-3246-7996-af0b-0548b351b9b3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashAndCashEquivalentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable_019cc527-3246-7c4a-906d-46cc8929fc60" xlink:to="loc_us-gaap_CashAndCashEquivalentsAxis_019cc527-3246-7996-af0b-0548b351b9b3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019cc527-3246-7996-af0b-0548b351b9b3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_019cc527-3246-7996-af0b-0548b351b9b3" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019cc527-3246-7996-af0b-0548b351b9b3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019cc527-3246-7721-83da-20b0817de344" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_019cc527-3246-7996-af0b-0548b351b9b3" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019cc527-3246-7721-83da-20b0817de344" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashMember_019cc527-3246-7914-8d0c-df71fcc3772a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019cc527-3246-7721-83da-20b0817de344" xlink:to="loc_us-gaap_CashMember_019cc527-3246-7914-8d0c-df71fcc3772a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_RestrictedCashMember_019cc527-3246-7ff6-a632-7691f3ae6c93" xlink:href="rigl-20260331.xsd#rigl_RestrictedCashMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019cc527-3246-7721-83da-20b0817de344" xlink:to="loc_rigl_RestrictedCashMember_019cc527-3246-7ff6-a632-7691f3ae6c93" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-79dd-9199-e397f771ef87" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable_019cc527-3246-7c4a-906d-46cc8929fc60" xlink:to="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-79dd-9199-e397f771ef87" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-79dd-9199-e397f771ef87_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-79dd-9199-e397f771ef87" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-79dd-9199-e397f771ef87_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70be-bad6-0e0ffdf0b8f4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-79dd-9199-e397f771ef87" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70be-bad6-0e0ffdf0b8f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_019cc527-3246-77db-9f6b-5a708a0739da" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70be-bad6-0e0ffdf0b8f4" xlink:to="loc_us-gaap_MoneyMarketFundsMember_019cc527-3246-77db-9f6b-5a708a0739da" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasuryBillSecuritiesMember_019cc527-3246-722d-8b38-04a74a714e15" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USTreasuryBillSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70be-bad6-0e0ffdf0b8f4" xlink:to="loc_us-gaap_USTreasuryBillSecuritiesMember_019cc527-3246-722d-8b38-04a74a714e15" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_019cc527-3246-71c2-ae0a-712d5cc889aa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70be-bad6-0e0ffdf0b8f4" xlink:to="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_019cc527-3246-71c2-ae0a-712d5cc889aa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CorporateBondSecuritiesAndCommercialPaperMember_019cc527-3246-7471-bb85-702cb1e10523" xlink:href="rigl-20260331.xsd#rigl_CorporateBondSecuritiesAndCommercialPaperMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70be-bad6-0e0ffdf0b8f4" xlink:to="loc_rigl_CorporateBondSecuritiesAndCommercialPaperMember_019cc527-3246-7471-bb85-702cb1e10523" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019cc527-3246-7666-9e39-ce9fd29f02a2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019cc527-3246-75d3-b08b-16302d53cfcb" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019cc527-3246-7666-9e39-ce9fd29f02a2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermInvestments_019cc527-3246-702d-aba0-6c67e749634a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShortTermInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019cc527-3246-75d3-b08b-16302d53cfcb" xlink:to="loc_us-gaap_ShortTermInvestments_019cc527-3246-702d-aba0-6c67e749634a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCash_019d6816-2048-7a51-a0a4-6785b91d2e8f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedCash"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019cc527-3246-75d3-b08b-16302d53cfcb" xlink:to="loc_us-gaap_RestrictedCash_019d6816-2048-7a51-a0a4-6785b91d2e8f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsAndShortTermInvestments_019cc527-3246-7f70-b4ef-6ed6fc75b3c6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashCashEquivalentsAndShortTermInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019cc527-3246-75d3-b08b-16302d53cfcb" xlink:to="loc_us-gaap_CashCashEquivalentsAndShortTermInvestments_019cc527-3246-7f70-b4ef-6ed6fc75b3c6" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/CashCashEquivalentsRestrictedCashandShortTermInvestmentsScheduleofCashEquivalentsandShortTermInvestmentsIncludingSecuritiesWithUnrealizedGainsandLossesDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#CashCashEquivalentsRestrictedCashandShortTermInvestmentsScheduleofCashEquivalentsandShortTermInvestmentsIncludingSecuritiesWithUnrealizedGainsandLossesDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/CashCashEquivalentsRestrictedCashandShortTermInvestmentsScheduleofCashEquivalentsandShortTermInvestmentsIncludingSecuritiesWithUnrealizedGainsandLossesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems_019cc527-3246-7040-a163-e01e2d3b857f" xlink:href="rigl-20260331.xsd#rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable_019cc527-3246-7445-9c09-43a28224c9ef" xlink:href="rigl-20260331.xsd#rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems_019cc527-3246-7040-a163-e01e2d3b857f" xlink:to="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable_019cc527-3246-7445-9c09-43a28224c9ef" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_019cc527-3246-7288-9f78-9403d005a44a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable_019cc527-3246-7445-9c09-43a28224c9ef" xlink:to="loc_us-gaap_FinancialInstrumentAxis_019cc527-3246-7288-9f78-9403d005a44a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019cc527-3246-7288-9f78-9403d005a44a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019cc527-3246-7288-9f78-9403d005a44a" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019cc527-3246-7288-9f78-9403d005a44a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019cc527-3246-7d9a-aca4-4c294fbf0f7e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019cc527-3246-7288-9f78-9403d005a44a" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019cc527-3246-7d9a-aca4-4c294fbf0f7e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasuryBillSecuritiesMember_019cc527-3246-7215-841e-bc71bf3f4962" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USTreasuryBillSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019cc527-3246-7d9a-aca4-4c294fbf0f7e" xlink:to="loc_us-gaap_USTreasuryBillSecuritiesMember_019cc527-3246-7215-841e-bc71bf3f4962" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_019cc527-3246-7519-9ae6-e3245a788d37" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019cc527-3246-7d9a-aca4-4c294fbf0f7e" xlink:to="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_019cc527-3246-7519-9ae6-e3245a788d37" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CorporateBondSecuritiesAndCommercialPaperMember_019cc527-3246-7a93-8e91-4eed6112a894" xlink:href="rigl-20260331.xsd#rigl_CorporateBondSecuritiesAndCommercialPaperMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019cc527-3246-7d9a-aca4-4c294fbf0f7e" xlink:to="loc_rigl_CorporateBondSecuritiesAndCommercialPaperMember_019cc527-3246-7a93-8e91-4eed6112a894" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostAfterAllowanceForCreditLoss_019d8b36-122c-76f9-8413-7bb06dabae01" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostAfterAllowanceForCreditLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems_019cc527-3246-7040-a163-e01e2d3b857f" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostAfterAllowanceForCreditLoss_019d8b36-122c-76f9-8413-7bb06dabae01" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019d87ca-6109-716b-b86c-1ba07d12615b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems_019cc527-3246-7040-a163-e01e2d3b857f" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019d87ca-6109-716b-b86c-1ba07d12615b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019d87ca-773f-7b8c-b917-f022f5246dab" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems_019cc527-3246-7040-a163-e01e2d3b857f" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019d87ca-773f-7b8c-b917-f022f5246dab" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019cc527-3246-7d03-81aa-3caea9de8db7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems_019cc527-3246-7040-a163-e01e2d3b857f" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019cc527-3246-7d03-81aa-3caea9de8db7" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/CashCashEquivalentsRestrictedCashandShortTermInvestmentsScheduleofFairValueandGrossUnrealizedLossesofOurInvestmentsDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#CashCashEquivalentsRestrictedCashandShortTermInvestmentsScheduleofFairValueandGrossUnrealizedLossesofOurInvestmentsDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/CashCashEquivalentsRestrictedCashandShortTermInvestmentsScheduleofFairValueandGrossUnrealizedLossesofOurInvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems_019cc527-3246-74f8-ae19-a2c441fdc6f0" xlink:href="rigl-20260331.xsd#rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable_019cc527-3246-774b-a2e3-9d36a8f33a87" xlink:href="rigl-20260331.xsd#rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems_019cc527-3246-74f8-ae19-a2c441fdc6f0" xlink:to="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable_019cc527-3246-774b-a2e3-9d36a8f33a87" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-7392-8097-38ed677fd94b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesTable_019cc527-3246-774b-a2e3-9d36a8f33a87" xlink:to="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-7392-8097-38ed677fd94b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-7392-8097-38ed677fd94b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-7392-8097-38ed677fd94b" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-7392-8097-38ed677fd94b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-7d96-9c94-362e1073eadf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-7392-8097-38ed677fd94b" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-7d96-9c94-362e1073eadf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasuryBillSecuritiesMember_019cc527-3246-72b6-8ee9-29ae2fb44c76" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USTreasuryBillSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-7d96-9c94-362e1073eadf" xlink:to="loc_us-gaap_USTreasuryBillSecuritiesMember_019cc527-3246-72b6-8ee9-29ae2fb44c76" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_019d1f91-e2fe-76b5-9f69-fbbff2c9e9d7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-7d96-9c94-362e1073eadf" xlink:to="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_019d1f91-e2fe-76b5-9f69-fbbff2c9e9d7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CorporateBondSecuritiesAndCommercialPaperMember_019d8b7b-0a6e-76bd-9e9b-7beaa4100f61" xlink:href="rigl-20260331.xsd#rigl_CorporateBondSecuritiesAndCommercialPaperMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-7d96-9c94-362e1073eadf" xlink:to="loc_rigl_CorporateBondSecuritiesAndCommercialPaperMember_019d8b7b-0a6e-76bd-9e9b-7beaa4100f61" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_019cc527-3246-76ca-8667-b3f63d96d48a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems_019cc527-3246-74f8-ae19-a2c441fdc6f0" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_019cc527-3246-76ca-8667-b3f63d96d48a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_019cc527-3246-7537-83c4-441105e473b8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_rigl_ScheduleOfCashAndCashEquivalentsAndAvailableForSaleSecuritiesLineItems_019cc527-3246-74f8-ae19-a2c441fdc6f0" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_019cc527-3246-7537-83c4-441105e473b8" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/FairValueScheduleofFinancialAssetsMeasuredatFairValueonaRecurringBasisDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#FairValueScheduleofFinancialAssetsMeasuredatFairValueonaRecurringBasisDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/FairValueScheduleofFinancialAssetsMeasuredatFairValueonaRecurringBasisDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019cc527-3246-7b5a-b9c7-0aff70c7f5d7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019cc527-3246-7767-98f7-67a38390c6fa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019cc527-3246-7b5a-b9c7-0aff70c7f5d7" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019cc527-3246-7767-98f7-67a38390c6fa" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019cc527-3246-74a4-85b0-990941775148" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019cc527-3246-7767-98f7-67a38390c6fa" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019cc527-3246-74a4-85b0-990941775148" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019cc527-3246-74a4-85b0-990941775148_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019cc527-3246-74a4-85b0-990941775148" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019cc527-3246-74a4-85b0-990941775148_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019cc527-3246-7187-99ff-3a61c6980e5a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019cc527-3246-74a4-85b0-990941775148" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019cc527-3246-7187-99ff-3a61c6980e5a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_019cc527-3246-7a2c-be25-f5047e973cb9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019cc527-3246-7187-99ff-3a61c6980e5a" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_019cc527-3246-7a2c-be25-f5047e973cb9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_019cc527-3246-7fe5-9d21-7581f9cbc3cb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019cc527-3246-7187-99ff-3a61c6980e5a" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_019cc527-3246-7fe5-9d21-7581f9cbc3cb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_019d1f96-49f2-7641-bf2f-650a0c4997f2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019cc527-3246-7187-99ff-3a61c6980e5a" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_019d1f96-49f2-7641-bf2f-650a0c4997f2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-7db1-bf66-bf9f844ea55b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019cc527-3246-7767-98f7-67a38390c6fa" xlink:to="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-7db1-bf66-bf9f844ea55b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-7db1-bf66-bf9f844ea55b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-7db1-bf66-bf9f844ea55b" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-7db1-bf66-bf9f844ea55b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70de-b748-9c5e6c31dbb3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentTypeCategorizationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_InvestmentTypeAxis_019cc527-3246-7db1-bf66-bf9f844ea55b" xlink:to="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70de-b748-9c5e6c31dbb3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_019cc527-3246-7022-8b63-bb3acc67f52f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70de-b748-9c5e6c31dbb3" xlink:to="loc_us-gaap_MoneyMarketFundsMember_019cc527-3246-7022-8b63-bb3acc67f52f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasuryBillSecuritiesMember_019cc527-3246-7d97-837a-0de1defbfa5e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USTreasuryBillSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70de-b748-9c5e6c31dbb3" xlink:to="loc_us-gaap_USTreasuryBillSecuritiesMember_019cc527-3246-7d97-837a-0de1defbfa5e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_019cc527-3246-7f9c-aa16-17018276614b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70de-b748-9c5e6c31dbb3" xlink:to="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_019cc527-3246-7f9c-aa16-17018276614b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CorporateBondSecuritiesAndCommercialPaperMember_019cc527-3246-7cd1-ad0c-714369179970" xlink:href="rigl-20260331.xsd#rigl_CorporateBondSecuritiesAndCommercialPaperMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentTypeCategorizationMember_019cc527-3246-70de-b748-9c5e6c31dbb3" xlink:to="loc_rigl_CorporateBondSecuritiesAndCommercialPaperMember_019cc527-3246-7cd1-ad0c-714369179970" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsFairValueDisclosure_019cc527-3246-71fa-a829-01d66128aa6f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019cc527-3246-7b5a-b9c7-0aff70c7f5d7" xlink:to="loc_us-gaap_InvestmentsFairValueDisclosure_019cc527-3246-71fa-a829-01d66128aa6f" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/DebtNarrativeDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#DebtNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/DebtNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_019cc527-3246-7402-b0df-577ee6890939" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_019cc527-3246-73b6-9130-37b3954b6d6d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019cc527-3246-7402-b0df-577ee6890939" xlink:to="loc_us-gaap_DebtInstrumentTable_019cc527-3246-73b6-9130-37b3954b6d6d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_019cc527-3246-7713-9165-a0ffd9c42683" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_019cc527-3246-73b6-9130-37b3954b6d6d" xlink:to="loc_us-gaap_CreditFacilityAxis_019cc527-3246-7713-9165-a0ffd9c42683" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_019cc527-3246-7713-9165-a0ffd9c42683_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_019cc527-3246-7713-9165-a0ffd9c42683" xlink:to="loc_us-gaap_CreditFacilityDomain_019cc527-3246-7713-9165-a0ffd9c42683_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_019cc527-3246-7091-8fc3-b2bb54d1df35" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_019cc527-3246-7713-9165-a0ffd9c42683" xlink:to="loc_us-gaap_CreditFacilityDomain_019cc527-3246-7091-8fc3-b2bb54d1df35" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_019cc527-3246-77ea-8eff-4a6167777472" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LineOfCreditMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_019cc527-3246-7091-8fc3-b2bb54d1df35" xlink:to="loc_us-gaap_LineOfCreditMember_019cc527-3246-77ea-8eff-4a6167777472" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateAxis_019d1fa8-364e-7c26-8040-e8663281a5ad" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VariableRateAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_019cc527-3246-73b6-9130-37b3954b6d6d" xlink:to="loc_us-gaap_VariableRateAxis_019d1fa8-364e-7c26-8040-e8663281a5ad" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateDomain_019d1fa8-364e-7c26-8040-e8663281a5ad_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VariableRateDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_VariableRateAxis_019d1fa8-364e-7c26-8040-e8663281a5ad" xlink:to="loc_us-gaap_VariableRateDomain_019d1fa8-364e-7c26-8040-e8663281a5ad_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateDomain_019d1fa8-364e-78ce-8563-572d07247a69" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VariableRateDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_VariableRateAxis_019d1fa8-364e-7c26-8040-e8663281a5ad" xlink:to="loc_us-gaap_VariableRateDomain_019d1fa8-364e-78ce-8563-572d07247a69" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_OneMonthSecuredOvernightFinancingRateSOFRMember_019d1fa8-83e4-7d49-aa44-d746eb693c57" xlink:href="rigl-20260331.xsd#rigl_OneMonthSecuredOvernightFinancingRateSOFRMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_019d1fa8-364e-78ce-8563-572d07247a69" xlink:to="loc_rigl_OneMonthSecuredOvernightFinancingRateSOFRMember_019d1fa8-83e4-7d49-aa44-d746eb693c57" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BaseRateMember_019d1fa8-d1ea-74a6-b283-c8a1f6bc1abf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_BaseRateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_019d1fa8-364e-78ce-8563-572d07247a69" xlink:to="loc_us-gaap_BaseRateMember_019d1fa8-d1ea-74a6-b283-c8a1f6bc1abf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuredOvernightFinancingRateSofrMember_019d1fa9-0bb9-7172-9dd0-3c4aca87f3bf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SecuredOvernightFinancingRateSofrMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_019d1fa8-364e-78ce-8563-572d07247a69" xlink:to="loc_us-gaap_SecuredOvernightFinancingRateSofrMember_019d1fa9-0bb9-7172-9dd0-3c4aca87f3bf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_019cc527-3246-7f6b-a966-3d761431c4f7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019cc527-3246-7402-b0df-577ee6890939" xlink:to="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_019cc527-3246-7f6b-a966-3d761431c4f7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_019cc527-3246-7e9e-b931-3d62c35b2619" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentBasisSpreadOnVariableRate1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019cc527-3246-7402-b0df-577ee6890939" xlink:to="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_019cc527-3246-7e9e-b931-3d62c35b2619" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPricePercentageOfPrincipalAmountRedeemed_019cc527-3246-744d-b2d8-de741c50832a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentRedemptionPricePercentageOfPrincipalAmountRedeemed"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019cc527-3246-7402-b0df-577ee6890939" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPricePercentageOfPrincipalAmountRedeemed_019cc527-3246-744d-b2d8-de741c50832a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebt_019d1fa5-5708-76c8-9db3-5dfa279f9294" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InterestExpenseDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019cc527-3246-7402-b0df-577ee6890939" xlink:to="loc_us-gaap_InterestExpenseDebt_019d1fa5-5708-76c8-9db3-5dfa279f9294" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityIncreaseAccruedInterest_019cc527-3246-7ddc-8085-0e4105221076" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LineOfCreditFacilityIncreaseAccruedInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019cc527-3246-7402-b0df-577ee6890939" xlink:to="loc_us-gaap_LineOfCreditFacilityIncreaseAccruedInterest_019cc527-3246-7ddc-8085-0e4105221076" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/CommitmentsandContingenciesDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#CommitmentsandContingenciesDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/CommitmentsandContingenciesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionLineItems_019cc527-3246-7272-b758-e074927a86b3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeLeaseDescriptionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionTable_019cc527-3246-755a-a3f7-0b1fb95a0854" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeLeaseDescriptionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019cc527-3246-7272-b758-e074927a86b3" xlink:to="loc_us-gaap_LesseeLeaseDescriptionTable_019cc527-3246-755a-a3f7-0b1fb95a0854" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019cc527-3246-7913-a72e-42fa70098722" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_019cc527-3246-755a-a3f7-0b1fb95a0854" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019cc527-3246-7913-a72e-42fa70098722" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019cc527-3246-7913-a72e-42fa70098722_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019cc527-3246-7913-a72e-42fa70098722" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019cc527-3246-7913-a72e-42fa70098722_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019cc527-3246-71bc-bf9e-467fb24d0d1d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019cc527-3246-7913-a72e-42fa70098722" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019cc527-3246-71bc-bf9e-467fb24d0d1d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_HeadquartersOfficeSpaceSubleaseSouthSanFranciscoCaliforniaMember_019cc527-3246-73c0-80c2-13db97a1cf0a" xlink:href="rigl-20260331.xsd#rigl_HeadquartersOfficeSpaceSubleaseSouthSanFranciscoCaliforniaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019cc527-3246-71bc-bf9e-467fb24d0d1d" xlink:to="loc_rigl_HeadquartersOfficeSpaceSubleaseSouthSanFranciscoCaliforniaMember_019cc527-3246-73c0-80c2-13db97a1cf0a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseCost_019d67f7-9dd1-707e-a7bf-dc4f8209f65a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019cc527-3246-7272-b758-e074927a86b3" xlink:to="loc_us-gaap_OperatingLeaseCost_019d67f7-9dd1-707e-a7bf-dc4f8209f65a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeasePayments_019cc527-3246-7500-9650-823295873700" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeasePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019cc527-3246-7272-b758-e074927a86b3" xlink:to="loc_us-gaap_OperatingLeasePayments_019cc527-3246-7500-9650-823295873700" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_019cc527-3246-78d5-89da-084ddfe1329b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019cc527-3246-7272-b758-e074927a86b3" xlink:to="loc_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_019cc527-3246-78d5-89da-084ddfe1329b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019d53f6-20ce-70ea-9592-ca1beb433eb1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019cc527-3246-7272-b758-e074927a86b3" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019d53f6-20ce-70ea-9592-ca1beb433eb1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_OffBalanceSheetContractualObligationsSubjectToCancellationFees_019d1fad-53a0-7746-864b-537658e88e49" xlink:href="rigl-20260331.xsd#rigl_OffBalanceSheetContractualObligationsSubjectToCancellationFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019cc527-3246-7272-b758-e074927a86b3" xlink:to="loc_rigl_OffBalanceSheetContractualObligationsSubjectToCancellationFees_019d1fad-53a0-7746-864b-537658e88e49" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_OffBalanceSheetContractualObligationsSubjectToCancellationFeesDueWithinOneYear_019d1fad-53a0-750f-8b20-f40632e79918" xlink:href="rigl-20260331.xsd#rigl_OffBalanceSheetContractualObligationsSubjectToCancellationFeesDueWithinOneYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019cc527-3246-7272-b758-e074927a86b3" xlink:to="loc_rigl_OffBalanceSheetContractualObligationsSubjectToCancellationFeesDueWithinOneYear_019d1fad-53a0-750f-8b20-f40632e79918" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_OffBalanceSheetContractualObligationsSubjectToCancellationFeesDueInSecondAndThirdYear_019d1fad-53a0-7166-854d-f5f7b76f560a" xlink:href="rigl-20260331.xsd#rigl_OffBalanceSheetContractualObligationsSubjectToCancellationFeesDueInSecondAndThirdYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019cc527-3246-7272-b758-e074927a86b3" xlink:to="loc_rigl_OffBalanceSheetContractualObligationsSubjectToCancellationFeesDueInSecondAndThirdYear_019d1fad-53a0-7166-854d-f5f7b76f560a" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CancellationFeesUnderAgreementsWithContractManufacturers_019d1fad-53a0-74e0-8753-830b6c00f21a" xlink:href="rigl-20260331.xsd#rigl_CancellationFeesUnderAgreementsWithContractManufacturers"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019cc527-3246-7272-b758-e074927a86b3" xlink:to="loc_rigl_CancellationFeesUnderAgreementsWithContractManufacturers_019d1fad-53a0-74e0-8753-830b6c00f21a" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/IncomeTaxesDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#IncomeTaxesDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/IncomeTaxesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EffectiveIncomeTaxRateReconciliationLineItems_019d1fc0-2254-784e-9e45-3ee4f902188e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EffectiveIncomeTaxRateReconciliationTable_019d1fc0-2254-7869-9235-ce849b11c9e7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EffectiveIncomeTaxRateReconciliationLineItems_019d1fc0-2254-784e-9e45-3ee4f902188e" xlink:to="loc_us-gaap_EffectiveIncomeTaxRateReconciliationTable_019d1fc0-2254-7869-9235-ce849b11c9e7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityAxis_019d1fc0-2254-76c6-87ce-917ad50d3b1f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeTaxAuthorityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_EffectiveIncomeTaxRateReconciliationTable_019d1fc0-2254-7869-9235-ce849b11c9e7" xlink:to="loc_us-gaap_IncomeTaxAuthorityAxis_019d1fc0-2254-76c6-87ce-917ad50d3b1f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_019d1fc0-2254-76c6-87ce-917ad50d3b1f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_019d1fc0-2254-76c6-87ce-917ad50d3b1f" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_019d1fc0-2254-76c6-87ce-917ad50d3b1f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_019d1fc0-2254-7970-a982-527b1a7d59bf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_019d1fc0-2254-76c6-87ce-917ad50d3b1f" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_019d1fc0-2254-7970-a982-527b1a7d59bf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DomesticCountryMember_019d8b3d-8ca9-74b9-a612-305654481859" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DomesticCountryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_019d1fc0-2254-7970-a982-527b1a7d59bf" xlink:to="loc_us-gaap_DomesticCountryMember_019d8b3d-8ca9-74b9-a612-305654481859" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_country_US_019d6805-5677-743b-a9a3-e79db05602fe" xlink:href="https://xbrl.sec.gov/country/2025/country-2025.xsd#country_US"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DomesticCountryMember_019d8b3d-8ca9-74b9-a612-305654481859" xlink:to="loc_country_US_019d6805-5677-743b-a9a3-e79db05602fe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StateAndLocalTaxJurisdictionOtherMember_019d1fc0-2254-74be-bbf0-c6a69801cb88" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StateAndLocalTaxJurisdictionOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DomesticCountryMember_019d8b3d-8ca9-74b9-a612-305654481859" xlink:to="loc_us-gaap_StateAndLocalTaxJurisdictionOtherMember_019d1fc0-2254-74be-bbf0-c6a69801cb88" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_019d1fc0-2254-7ea1-aca4-b1da0e0c45b0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EffectiveIncomeTaxRateReconciliationLineItems_019d1fc0-2254-784e-9e45-3ee4f902188e" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_019d1fc0-2254-7ea1-aca4-b1da0e0c45b0" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/SegmentInformationDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#SegmentInformationDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/SegmentInformationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationLineItems_019cc527-3246-741d-8488-2fea2a9bdde8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentReportingInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019cc527-3246-70e6-a593-fadb759777d7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019cc527-3246-741d-8488-2fea2a9bdde8" xlink:to="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019cc527-3246-70e6-a593-fadb759777d7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_019cc527-3246-7d23-8f69-a9566821746d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019cc527-3246-70e6-a593-fadb759777d7" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_019cc527-3246-7d23-8f69-a9566821746d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_019cc527-3246-7d23-8f69-a9566821746d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_019cc527-3246-7d23-8f69-a9566821746d" xlink:to="loc_us-gaap_SegmentDomain_019cc527-3246-7d23-8f69-a9566821746d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_019cc527-3246-79db-afac-6df22102fa4d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_019cc527-3246-7d23-8f69-a9566821746d" xlink:to="loc_us-gaap_SegmentDomain_019cc527-3246-79db-afac-6df22102fa4d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_OneOperatingSegmentMember_019cc527-3246-76b2-bed8-cc133d28c2ad" xlink:href="rigl-20260331.xsd#rigl_OneOperatingSegmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_019cc527-3246-79db-afac-6df22102fa4d" xlink:to="loc_rigl_OneOperatingSegmentMember_019cc527-3246-76b2-bed8-cc133d28c2ad" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NumberOfReportableSegments_019cc527-3246-79e1-94bf-2fe709ce02c7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NumberOfReportableSegments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019cc527-3246-741d-8488-2fea2a9bdde8" xlink:to="loc_us-gaap_NumberOfReportableSegments_019cc527-3246-79e1-94bf-2fe709ce02c7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019cc527-3246-7c3b-86a0-dfaf55424efd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019cc527-3246-741d-8488-2fea2a9bdde8" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019cc527-3246-7c3b-86a0-dfaf55424efd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3246-7a49-85bf-b6d92fb61c1a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostsAndExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019cc527-3246-741d-8488-2fea2a9bdde8" xlink:to="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3246-7a49-85bf-b6d92fb61c1a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LaborAndRelatedExpense_019cc527-3246-786d-8e80-f0e0a4f9011c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LaborAndRelatedExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3246-7a49-85bf-b6d92fb61c1a" xlink:to="loc_us-gaap_LaborAndRelatedExpense_019cc527-3246-786d-8e80-f0e0a4f9011c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_CommercialRelatedExpenses_019cc527-3246-7f5a-8514-3c1a8095e29c" xlink:href="rigl-20260331.xsd#rigl_CommercialRelatedExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3246-7a49-85bf-b6d92fb61c1a" xlink:to="loc_rigl_CommercialRelatedExpenses_019cc527-3246-7f5a-8514-3c1a8095e29c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_OutsideClinicalTrialRelatedExpenses_019cc527-3246-7db9-94ed-b87383a2f1d4" xlink:href="rigl-20260331.xsd#rigl_OutsideClinicalTrialRelatedExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3246-7a49-85bf-b6d92fb61c1a" xlink:to="loc_rigl_OutsideClinicalTrialRelatedExpenses_019cc527-3246-7db9-94ed-b87383a2f1d4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_019cc527-3246-7a56-b0f1-d0d26168e072" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3246-7a49-85bf-b6d92fb61c1a" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_019cc527-3246-7a56-b0f1-d0d26168e072" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_ConsultantsAndThirdPartyServicesExpense_019cc527-3246-7299-8fdb-cdcffac6f643" xlink:href="rigl-20260331.xsd#rigl_ConsultantsAndThirdPartyServicesExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3246-7a49-85bf-b6d92fb61c1a" xlink:to="loc_rigl_ConsultantsAndThirdPartyServicesExpense_019cc527-3246-7299-8fdb-cdcffac6f643" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingOtherItemAmount_019cc527-3246-7ce8-8ea4-d48bf9ff3038" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentReportingOtherItemAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3246-7a49-85bf-b6d92fb61c1a" xlink:to="loc_us-gaap_SegmentReportingOtherItemAmount_019cc527-3246-7ce8-8ea4-d48bf9ff3038" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestIncomeExpenseNet_019cc527-3246-7c9c-a767-70008b204f55" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InterestIncomeExpenseNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3246-7a49-85bf-b6d92fb61c1a" xlink:to="loc_us-gaap_InterestIncomeExpenseNet_019cc527-3246-7c9c-a767-70008b204f55" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_019cc527-3246-7aa8-aca5-d440a4c2976d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_019cc527-3246-7a49-85bf-b6d92fb61c1a" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_019cc527-3246-7aa8-aca5-d440a4c2976d" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019cc527-3246-712b-95c8-d328cebffa1a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019cc527-3246-741d-8488-2fea2a9bdde8" xlink:to="loc_us-gaap_NetIncomeLoss_019cc527-3246-712b-95c8-d328cebffa1a" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.rigel.com/role/SubsequentEventsDetails" xlink:type="simple" xlink:href="rigl-20260331.xsd#SubsequentEventsDetails"/>
  <link:definitionLink xlink:role="http://www.rigel.com/role/SubsequentEventsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventLineItems_019d9ba9-a776-70c4-a19d-e0dd9499f216" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTable_019d9ba9-a776-7c60-8172-40ee73d547d0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsequentEventLineItems_019d9ba9-a776-70c4-a19d-e0dd9499f216" xlink:to="loc_us-gaap_SubsequentEventTable_019d9ba9-a776-7c60-8172-40ee73d547d0" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_019d9ba9-a776-7fc0-a556-8d715ac36ef1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_019d9ba9-a776-7c60-8172-40ee73d547d0" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_019d9ba9-a776-7fc0-a556-8d715ac36ef1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_019d9ba9-a776-7fc0-a556-8d715ac36ef1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_019d9ba9-a776-7fc0-a556-8d715ac36ef1" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_019d9ba9-a776-7fc0-a556-8d715ac36ef1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_019d9ba9-a776-7a59-9c40-043a627f4bcb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_019d9ba9-a776-7fc0-a556-8d715ac36ef1" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_019d9ba9-a776-7a59-9c40-043a627f4bcb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_019d9ba9-a776-7e53-b486-4c7d64c81c59" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_019d9ba9-a776-7a59-9c40-043a627f4bcb" xlink:to="loc_us-gaap_SubsequentEventMember_019d9ba9-a776-7e53-b486-4c7d64c81c59" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_019d9ba9-a776-75ee-ba13-6d7c412cb9dd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_019d9ba9-a776-7c60-8172-40ee73d547d0" xlink:to="loc_us-gaap_CreditFacilityAxis_019d9ba9-a776-75ee-ba13-6d7c412cb9dd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_019d9ba9-a776-75ee-ba13-6d7c412cb9dd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_019d9ba9-a776-75ee-ba13-6d7c412cb9dd" xlink:to="loc_us-gaap_CreditFacilityDomain_019d9ba9-a776-75ee-ba13-6d7c412cb9dd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_019d9ba9-a776-7b26-901d-e2c8cb018336" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_019d9ba9-a776-75ee-ba13-6d7c412cb9dd" xlink:to="loc_us-gaap_CreditFacilityDomain_019d9ba9-a776-7b26-901d-e2c8cb018336" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_019d9ba9-a776-77c7-b538-fccd3d3a8ba7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LineOfCreditMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_019d9ba9-a776-7b26-901d-e2c8cb018336" xlink:to="loc_us-gaap_LineOfCreditMember_019d9ba9-a776-77c7-b538-fccd3d3a8ba7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateAxis_019d9ba9-a776-7a72-8d10-4e230d589997" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VariableRateAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_019d9ba9-a776-7c60-8172-40ee73d547d0" xlink:to="loc_us-gaap_VariableRateAxis_019d9ba9-a776-7a72-8d10-4e230d589997" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateDomain_019d9ba9-a776-7a72-8d10-4e230d589997_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VariableRateDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_VariableRateAxis_019d9ba9-a776-7a72-8d10-4e230d589997" xlink:to="loc_us-gaap_VariableRateDomain_019d9ba9-a776-7a72-8d10-4e230d589997_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateDomain_019d9ba9-a776-7b90-b8cf-1ad197eb2c2e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VariableRateDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_VariableRateAxis_019d9ba9-a776-7a72-8d10-4e230d589997" xlink:to="loc_us-gaap_VariableRateDomain_019d9ba9-a776-7b90-b8cf-1ad197eb2c2e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BaseRateMember_019db952-6986-7895-ad14-7c78b13046b1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_BaseRateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_019d9ba9-a776-7b90-b8cf-1ad197eb2c2e" xlink:to="loc_us-gaap_BaseRateMember_019db952-6986-7895-ad14-7c78b13046b1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuredOvernightFinancingRateSofrMember_019db950-bcdb-7dac-a19f-1c74d12b1fa7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SecuredOvernightFinancingRateSofrMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_019d9ba9-a776-7b90-b8cf-1ad197eb2c2e" xlink:to="loc_us-gaap_SecuredOvernightFinancingRateSofrMember_019db950-bcdb-7dac-a19f-1c74d12b1fa7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_019d9bb1-6489-71af-b1bb-49f761b5b0b8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_019d9ba9-a776-70c4-a19d-e0dd9499f216" xlink:to="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_019d9bb1-6489-71af-b1bb-49f761b5b0b8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_rigl_LineOfCreditFacilityAccordionFeatureHigherBorrowingCapacityOption_019db955-4026-7907-9e91-39ea92cf145b" xlink:href="rigl-20260331.xsd#rigl_LineOfCreditFacilityAccordionFeatureHigherBorrowingCapacityOption"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_019d9ba9-a776-70c4-a19d-e0dd9499f216" xlink:to="loc_rigl_LineOfCreditFacilityAccordionFeatureHigherBorrowingCapacityOption_019db955-4026-7907-9e91-39ea92cf145b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtTerm_019d9bcc-638b-7269-8e67-b3d5e0a42825" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongTermDebtTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_019d9ba9-a776-70c4-a19d-e0dd9499f216" xlink:to="loc_us-gaap_LongTermDebtTerm_019d9bcc-638b-7269-8e67-b3d5e0a42825" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_019d9ba9-a776-7aad-b6ed-9b7b409b774d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_019d9ba9-a776-70c4-a19d-e0dd9499f216" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_019d9ba9-a776-7aad-b6ed-9b7b409b774d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_019d9ba9-a776-71c4-95ac-076f3650f892" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentBasisSpreadOnVariableRate1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_019d9ba9-a776-70c4-a19d-e0dd9499f216" xlink:to="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_019d9ba9-a776-71c4-95ac-076f3650f892" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCredit_019d9bc8-55ed-7b72-b860-88aa514bbd59" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LineOfCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_019d9ba9-a776-70c4-a19d-e0dd9499f216" xlink:to="loc_us-gaap_LineOfCredit_019d9bc8-55ed-7b72-b860-88aa514bbd59" xlink:type="arc" order="5"/>
  </link:definitionLink>
</link:linkbase>
