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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019e6b08-e92f-7f01-8bea-f07579db4b24,g:dea06e73-5514-454c-8136-edf5adaa5e89-->
<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.delcath.com/role/CondensedConsolidatedStatementsofStockholdersEquityUnaudited" xlink:type="simple" xlink:href="dcth-20260630.xsd#CondensedConsolidatedStatementsofStockholdersEquityUnaudited"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/CondensedConsolidatedStatementsofStockholdersEquityUnaudited" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019e6b08-e9fd-7db8-b9d2-78317744100e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019e6b08-e9fd-7e87-864c-2a53c61b6cb5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019e6b08-e9fd-7db8-b9d2-78317744100e" xlink:to="loc_us-gaap_StatementTable_019e6b08-e9fd-7e87-864c-2a53c61b6cb5" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_019e6b08-e9fd-7373-ada4-e1584f5d4e41" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019e6b08-e9fd-7e87-864c-2a53c61b6cb5" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_019e6b08-e9fd-7373-ada4-e1584f5d4e41" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019e6b08-e9fd-7373-ada4-e1584f5d4e41_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019e6b08-e9fd-7373-ada4-e1584f5d4e41" xlink:to="loc_us-gaap_EquityComponentDomain_019e6b08-e9fd-7373-ada4-e1584f5d4e41_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019e6b08-e9fd-739b-8c2e-df1800e675f3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019e6b08-e9fd-7373-ada4-e1584f5d4e41" xlink:to="loc_us-gaap_EquityComponentDomain_019e6b08-e9fd-739b-8c2e-df1800e675f3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockMember_019e6b08-e9fd-7554-b44c-52931c974793" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019e6b08-e9fd-739b-8c2e-df1800e675f3" xlink:to="loc_us-gaap_PreferredStockMember_019e6b08-e9fd-7554-b44c-52931c974793" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_019e6b08-e9fd-78e6-aff8-9c2475a80102" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019e6b08-e9fd-739b-8c2e-df1800e675f3" xlink:to="loc_us-gaap_CommonStockMember_019e6b08-e9fd-78e6-aff8-9c2475a80102" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_019e6b08-e9fd-7646-ac64-56020cd548ca" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019e6b08-e9fd-739b-8c2e-df1800e675f3" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_019e6b08-e9fd-7646-ac64-56020cd548ca" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_019e6b08-e9fd-78c3-ba91-65ea9c22b57a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019e6b08-e9fd-739b-8c2e-df1800e675f3" xlink:to="loc_us-gaap_RetainedEarningsMember_019e6b08-e9fd-78c3-ba91-65ea9c22b57a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019e6b08-e9fd-7400-8901-86144b673995" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019e6b08-e9fd-739b-8c2e-df1800e675f3" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019e6b08-e9fd-7400-8901-86144b673995" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e6b08-e9fd-7eda-9f9a-6ee5ed402df6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019e6b08-e9fd-7e87-864c-2a53c61b6cb5" xlink:to="loc_us-gaap_AwardTypeAxis_019e6b08-e9fd-7eda-9f9a-6ee5ed402df6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e6b08-e9fd-7eda-9f9a-6ee5ed402df6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e6b08-e9fd-7eda-9f9a-6ee5ed402df6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e6b08-e9fd-7eda-9f9a-6ee5ed402df6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e6b08-e9fd-7f3f-9cfe-66000e77735c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e6b08-e9fd-7eda-9f9a-6ee5ed402df6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e6b08-e9fd-7f3f-9cfe-66000e77735c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_019e6b08-e9fd-7971-9890-49de5e55b514" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e6b08-e9fd-7f3f-9cfe-66000e77735c" xlink:to="loc_us-gaap_EmployeeStockOptionMember_019e6b08-e9fd-7971-9890-49de5e55b514" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_019e6b08-e9fd-73e8-9acd-dee0f8545bc5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e6b08-e9fd-7f3f-9cfe-66000e77735c" xlink:to="loc_us-gaap_EmployeeStockMember_019e6b08-e9fd-73e8-9acd-dee0f8545bc5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-77a8-a271-b3c353210168" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019e6b08-e9fd-7e87-864c-2a53c61b6cb5" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-77a8-a271-b3c353210168" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-77a8-a271-b3c353210168_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-77a8-a271-b3c353210168" xlink:to="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-77a8-a271-b3c353210168_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7e18-95b4-e93c8494633e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-77a8-a271-b3c353210168" xlink:to="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7e18-95b4-e93c8494633e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesFPreferredStockMember_019e6b08-e9fd-78d6-aae4-dc34f451c95a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeriesFPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7e18-95b4-e93c8494633e" xlink:to="loc_us-gaap_SeriesFPreferredStockMember_019e6b08-e9fd-78d6-aae4-dc34f451c95a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019e6b08-e9fd-7db8-b9d2-78317744100e" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_019e6b08-e9fd-7b1e-87a8-37ef96a2e1f5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_SharesOutstanding_019e6b08-e9fd-7b1e-87a8-37ef96a2e1f5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019e6b08-e9fd-7d23-84cc-8b1d1480508b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_StockholdersEquity_019e6b08-e9fd-7d23-84cc-8b1d1480508b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalShareBasedCompensationStockOptionsRequisiteServicePeriodRecognition_019e6b08-e9fd-7b00-9ba3-08856f86ed44" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalShareBasedCompensationStockOptionsRequisiteServicePeriodRecognition"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalShareBasedCompensationStockOptionsRequisiteServicePeriodRecognition_019e6b08-e9fd-7b00-9ba3-08856f86ed44" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_019e6b08-e9fd-7c88-913f-c89a805e89f2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_019e6b08-e9fd-7c88-913f-c89a805e89f2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_019e6b08-e9fd-7ae7-95a7-0d4b10155de1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_019e6b08-e9fd-7ae7-95a7-0d4b10155de1" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_StockIssuedDuringPeriodSharesExerciseOfWarrants_019e6b08-e9fd-7a66-84b5-8bdb8dc52b56" xlink:href="dcth-20260630.xsd#dcth_StockIssuedDuringPeriodSharesExerciseOfWarrants"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_dcth_StockIssuedDuringPeriodSharesExerciseOfWarrants_019e6b08-e9fd-7a66-84b5-8bdb8dc52b56" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_StockIssuedDuringPeriodValueExerciseOfWarrants_019e6b08-e9fd-7da4-8809-ff0da8e29404" xlink:href="dcth-20260630.xsd#dcth_StockIssuedDuringPeriodValueExerciseOfWarrants"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_dcth_StockIssuedDuringPeriodValueExerciseOfWarrants_019e6b08-e9fd-7da4-8809-ff0da8e29404" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019e6b08-e9fd-7d31-8f3e-06aaec365032" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019e6b08-e9fd-7d31-8f3e-06aaec365032" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_019e6b08-e9fd-75b4-a070-be993f26ace8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_019e6b08-e9fd-75b4-a070-be993f26ace8" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_019e6b08-e9fd-7e31-9c1b-52e5de137354" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockRepurchasedAndRetiredDuringPeriodShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_019e6b08-e9fd-7e31-9c1b-52e5de137354" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_019e6b08-e9fd-71a6-8318-0c2521bb6bef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockRepurchasedAndRetiredDuringPeriodValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_019e6b08-e9fd-71a6-8318-0c2521bb6bef" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019e6b08-e9fd-7000-a00f-e3b525ab00a6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_NetIncomeLoss_019e6b08-e9fd-7000-a00f-e3b525ab00a6" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_019e6b08-e9fd-77f8-988d-ef411993677b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_019e6b08-e9fd-77f8-988d-ef411993677b" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_019e6b08-e9fd-712a-a77b-fe59377fa5d7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e6b08-e9fd-740b-9026-79388feeb5d0" xlink:to="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_019e6b08-e9fd-712a-a77b-fe59377fa5d7" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_019e6b08-e9fd-7043-bc34-792a0bad536e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019e6b08-e9fd-7094-867e-481a42595b99" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/GeneralDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#GeneralDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/GeneralDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesLineItems_019e6b08-e9fd-7453-9f74-6f3fa69c8d8d" xlink:href="dcth-20260630.xsd#dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTable_019e6b08-e9fd-732c-a067-e673c8022705" xlink:href="dcth-20260630.xsd#dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesLineItems_019e6b08-e9fd-7453-9f74-6f3fa69c8d8d" xlink:to="loc_dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTable_019e6b08-e9fd-732c-a067-e673c8022705" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019e6b08-e9fd-7c66-92f3-1a838d27110e" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTable_019e6b08-e9fd-732c-a067-e673c8022705" xlink:to="loc_srt_ProductOrServiceAxis_019e6b08-e9fd-7c66-92f3-1a838d27110e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-7c66-92f3-1a838d27110e_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019e6b08-e9fd-7c66-92f3-1a838d27110e" xlink:to="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-7c66-92f3-1a838d27110e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-7b8b-8888-016047cc47ab" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019e6b08-e9fd-7c66-92f3-1a838d27110e" xlink:to="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-7b8b-8888-016047cc47ab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_HEPZATOKITMember_019e6b08-e9fd-718d-bfdd-a97483d3b104" xlink:href="dcth-20260630.xsd#dcth_HEPZATOKITMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-7b8b-8888-016047cc47ab" xlink:to="loc_dcth_HEPZATOKITMember_019e6b08-e9fd-718d-bfdd-a97483d3b104" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_HEPZATOKITMelphalanMember_019e6b08-e9fd-7637-b330-7cbdc959262e" xlink:href="dcth-20260630.xsd#dcth_HEPZATOKITMelphalanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-7b8b-8888-016047cc47ab" xlink:to="loc_dcth_HEPZATOKITMelphalanMember_019e6b08-e9fd-7637-b330-7cbdc959262e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_HEPZATOKITDoxorubicinMember_019e6b08-e9fd-7fb5-b564-112f92c07c98" xlink:href="dcth-20260630.xsd#dcth_HEPZATOKITDoxorubicinMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-7b8b-8888-016047cc47ab" xlink:to="loc_dcth_HEPZATOKITDoxorubicinMember_019e6b08-e9fd-7fb5-b564-112f92c07c98" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_CHEMOSATMember_019e6b08-e9fd-7c73-ace5-0ea46a86c70c" xlink:href="dcth-20260630.xsd#dcth_CHEMOSATMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-7b8b-8888-016047cc47ab" xlink:to="loc_dcth_CHEMOSATMember_019e6b08-e9fd-7c73-ace5-0ea46a86c70c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_NumberOfOrphanDrugDesignationsGrantedByUSFoodAndDrugAdministration_019e6b08-e9fd-70d2-8baf-46051c48313e" xlink:href="dcth-20260630.xsd#dcth_NumberOfOrphanDrugDesignationsGrantedByUSFoodAndDrugAdministration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesLineItems_019e6b08-e9fd-7453-9f74-6f3fa69c8d8d" xlink:to="loc_dcth_NumberOfOrphanDrugDesignationsGrantedByUSFoodAndDrugAdministration_019e6b08-e9fd-70d2-8baf-46051c48313e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ProductReimbursementPeriod_019e6b08-e9fd-7c1b-b3cb-51cd8a1b2fc9" xlink:href="dcth-20260630.xsd#dcth_ProductReimbursementPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesLineItems_019e6b08-e9fd-7453-9f74-6f3fa69c8d8d" xlink:to="loc_dcth_ProductReimbursementPeriod_019e6b08-e9fd-7c1b-b3cb-51cd8a1b2fc9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClinicalTrialNumberOfPatients_019e6b08-e9fd-7cc8-b951-d075f8658a52" xlink:href="dcth-20260630.xsd#dcth_ClinicalTrialNumberOfPatients"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesLineItems_019e6b08-e9fd-7453-9f74-6f3fa69c8d8d" xlink:to="loc_dcth_ClinicalTrialNumberOfPatients_019e6b08-e9fd-7cc8-b951-d075f8658a52" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClinicalTrialNumberOfSites_019e6b08-e9fd-718b-a0c2-85829f1698dc" xlink:href="dcth-20260630.xsd#dcth_ClinicalTrialNumberOfSites"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesLineItems_019e6b08-e9fd-7453-9f74-6f3fa69c8d8d" xlink:to="loc_dcth_ClinicalTrialNumberOfSites_019e6b08-e9fd-718b-a0c2-85829f1698dc" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_019e6b08-e9fd-7802-8fe9-d189d91256e6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesLineItems_019e6b08-e9fd-7453-9f74-6f3fa69c8d8d" xlink:to="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_019e6b08-e9fd-7802-8fe9-d189d91256e6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_019e6b08-e9fd-72df-b870-6777016c64d4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesLineItems_019e6b08-e9fd-7453-9f74-6f3fa69c8d8d" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_019e6b08-e9fd-72df-b870-6777016c64d4" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/RevenueScheduleofRevenuebyProductDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#RevenueScheduleofRevenuebyProductDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/RevenueScheduleofRevenuebyProductDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_019e6b08-e9fd-7b9d-93f2-6b3518d62cd7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_019e6b08-e9fd-7735-8f9d-62c216660ab7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019e6b08-e9fd-7b9d-93f2-6b3518d62cd7" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_019e6b08-e9fd-7735-8f9d-62c216660ab7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019e6b08-e9fd-7343-ae2a-a2ebf6d55863" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019e6b08-e9fd-7735-8f9d-62c216660ab7" xlink:to="loc_srt_ProductOrServiceAxis_019e6b08-e9fd-7343-ae2a-a2ebf6d55863" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-7343-ae2a-a2ebf6d55863_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019e6b08-e9fd-7343-ae2a-a2ebf6d55863" xlink:to="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-7343-ae2a-a2ebf6d55863_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-70cc-aad1-382d3e7d6cc6" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019e6b08-e9fd-7343-ae2a-a2ebf6d55863" xlink:to="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-70cc-aad1-382d3e7d6cc6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_CHEMOSATMember_019e6b08-e9fd-7256-9794-cca897f0e844" xlink:href="dcth-20260630.xsd#dcth_CHEMOSATMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-70cc-aad1-382d3e7d6cc6" xlink:to="loc_dcth_CHEMOSATMember_019e6b08-e9fd-7256-9794-cca897f0e844" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_HEPZATOKITMember_019e6b08-e9fd-733e-8716-2f122d5b289f" xlink:href="dcth-20260630.xsd#dcth_HEPZATOKITMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019e6b08-e9fd-70cc-aad1-382d3e7d6cc6" xlink:to="loc_dcth_HEPZATOKITMember_019e6b08-e9fd-733e-8716-2f122d5b289f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019e6b08-e9fd-7d1c-b62f-ce3f0b2b683f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019e6b08-e9fd-7b9d-93f2-6b3518d62cd7" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019e6b08-e9fd-7d1c-b62f-ce3f0b2b683f" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/RevenueScheduleofRevenueandAccountsReceivableConcentrationsDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#RevenueScheduleofRevenueandAccountsReceivableConcentrationsDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/RevenueScheduleofRevenueandAccountsReceivableConcentrationsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_019e6b08-e9fd-7b03-945b-30a6d1229e13" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_019e6b08-e9fd-7869-b220-3b5a0df0ad06" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019e6b08-e9fd-7b03-945b-30a6d1229e13" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_019e6b08-e9fd-7869-b220-3b5a0df0ad06" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_019e6b08-e9fd-7fb0-b346-4d7f68d13bc2" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019e6b08-e9fd-7869-b220-3b5a0df0ad06" xlink:to="loc_srt_MajorCustomersAxis_019e6b08-e9fd-7fb0-b346-4d7f68d13bc2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_019e6b08-e9fd-7fb0-b346-4d7f68d13bc2_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_019e6b08-e9fd-7fb0-b346-4d7f68d13bc2" xlink:to="loc_srt_NameOfMajorCustomerDomain_019e6b08-e9fd-7fb0-b346-4d7f68d13bc2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_019e6b08-e9fd-7c0c-b3ea-35377b49408f" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_019e6b08-e9fd-7fb0-b346-4d7f68d13bc2" xlink:to="loc_srt_NameOfMajorCustomerDomain_019e6b08-e9fd-7c0c-b3ea-35377b49408f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_CustomerOneMember_019e6b08-e9fd-7cbe-8427-5614fdb54ba2" xlink:href="dcth-20260630.xsd#dcth_CustomerOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_019e6b08-e9fd-7c0c-b3ea-35377b49408f" xlink:to="loc_dcth_CustomerOneMember_019e6b08-e9fd-7cbe-8427-5614fdb54ba2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_CustomerTwoMember_019e6b08-e9fd-724a-84f9-efb3e8a77731" xlink:href="dcth-20260630.xsd#dcth_CustomerTwoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_019e6b08-e9fd-7c0c-b3ea-35377b49408f" xlink:to="loc_dcth_CustomerTwoMember_019e6b08-e9fd-724a-84f9-efb3e8a77731" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_CustomerThreeMember_019e6b08-e9fd-7a3e-8144-40b13f7ba952" xlink:href="dcth-20260630.xsd#dcth_CustomerThreeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_019e6b08-e9fd-7c0c-b3ea-35377b49408f" xlink:to="loc_dcth_CustomerThreeMember_019e6b08-e9fd-7a3e-8144-40b13f7ba952" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019e6b08-e9fd-7087-9f6f-d70dc3c74488" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019e6b08-e9fd-7869-b220-3b5a0df0ad06" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019e6b08-e9fd-7087-9f6f-d70dc3c74488" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019e6b08-e9fd-7087-9f6f-d70dc3c74488_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019e6b08-e9fd-7087-9f6f-d70dc3c74488" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019e6b08-e9fd-7087-9f6f-d70dc3c74488_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019e6b08-e9fd-7bb0-821b-7ace1a6d157a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019e6b08-e9fd-7087-9f6f-d70dc3c74488" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019e6b08-e9fd-7bb0-821b-7ace1a6d157a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerMember_019e6b08-e9fd-7025-92ac-c58aba7d3505" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019e6b08-e9fd-7bb0-821b-7ace1a6d157a" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerMember_019e6b08-e9fd-7025-92ac-c58aba7d3505" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableMember_019e6b08-e9fd-7a0e-93aa-dc0329b053ef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccountsReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019e6b08-e9fd-7bb0-821b-7ace1a6d157a" xlink:to="loc_us-gaap_AccountsReceivableMember_019e6b08-e9fd-7a0e-93aa-dc0329b053ef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_019e6b08-e9fd-78c5-9aaa-350cbd398148" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019e6b08-e9fd-7869-b220-3b5a0df0ad06" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_019e6b08-e9fd-78c5-9aaa-350cbd398148" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_019e6b08-e9fd-78c5-9aaa-350cbd398148_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_019e6b08-e9fd-78c5-9aaa-350cbd398148" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_019e6b08-e9fd-78c5-9aaa-350cbd398148_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_019e6b08-e9fd-7311-afe9-fb5c9b57b521" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_019e6b08-e9fd-78c5-9aaa-350cbd398148" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_019e6b08-e9fd-7311-afe9-fb5c9b57b521" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerConcentrationRiskMember_019e6b08-e9fd-7215-b58f-58e1cdc9cc8a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CustomerConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_019e6b08-e9fd-7311-afe9-fb5c9b57b521" xlink:to="loc_us-gaap_CustomerConcentrationRiskMember_019e6b08-e9fd-7215-b58f-58e1cdc9cc8a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_019e6b08-e9fd-7b1f-84a7-f462250184c4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019e6b08-e9fd-7b03-945b-30a6d1229e13" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_019e6b08-e9fd-7b1f-84a7-f462250184c4" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/InvestmentsDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#InvestmentsDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/InvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e6b08-e9fd-718f-bf80-c5f6a045d4d4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019e6b08-e9fd-7a6f-b9f1-8599e7adc454" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e6b08-e9fd-718f-bf80-c5f6a045d4d4" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019e6b08-e9fd-7a6f-b9f1-8599e7adc454" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_019e6b08-e9fd-7573-ab08-fb7e0bd7caf5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019e6b08-e9fd-7a6f-b9f1-8599e7adc454" xlink:to="loc_us-gaap_FinancialInstrumentAxis_019e6b08-e9fd-7573-ab08-fb7e0bd7caf5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019e6b08-e9fd-7573-ab08-fb7e0bd7caf5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019e6b08-e9fd-7573-ab08-fb7e0bd7caf5" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019e6b08-e9fd-7573-ab08-fb7e0bd7caf5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019e6b08-e9fd-7577-a345-da88afb4a7c6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019e6b08-e9fd-7573-ab08-fb7e0bd7caf5" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019e6b08-e9fd-7577-a345-da88afb4a7c6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_019e6b08-e9fd-7b89-9d62-7ea0edc57a42" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019e6b08-e9fd-7577-a345-da88afb4a7c6" xlink:to="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_019e6b08-e9fd-7b89-9d62-7ea0edc57a42" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019e6b08-e9fd-7e27-bf78-ac11e78473e3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e6b08-e9fd-718f-bf80-c5f6a045d4d4" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_019e6b08-e9fd-7e27-bf78-ac11e78473e3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019e6b08-e9fd-75d4-93a9-526e58436ad3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e6b08-e9fd-718f-bf80-c5f6a045d4d4" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019e6b08-e9fd-75d4-93a9-526e58436ad3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_019e6b08-e9fd-7156-bd34-8601c9d39daa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e6b08-e9fd-718f-bf80-c5f6a045d4d4" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_019e6b08-e9fd-7156-bd34-8601c9d39daa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestReceivableCurrent_019e6b08-e9fd-7824-b64b-0dad73f5acff" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestReceivableCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e6b08-e9fd-718f-bf80-c5f6a045d4d4" xlink:to="loc_us-gaap_InterestReceivableCurrent_019e6b08-e9fd-7824-b64b-0dad73f5acff" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/InventoryNarrativeDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#InventoryNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/InventoryNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryLineItems_019e6b08-e9fd-717e-8a2c-8c10d1811dc8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InventoryLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryCurrentTable_019e6b08-e9fd-7f8d-8e65-f43984cedc7b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InventoryCurrentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_InventoryLineItems_019e6b08-e9fd-717e-8a2c-8c10d1811dc8" xlink:to="loc_us-gaap_InventoryCurrentTable_019e6b08-e9fd-7f8d-8e65-f43984cedc7b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PublicUtilitiesInventoryAxis_019e6b08-e9fd-79d7-b14b-5271efa57faa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PublicUtilitiesInventoryAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_InventoryCurrentTable_019e6b08-e9fd-7f8d-8e65-f43984cedc7b" xlink:to="loc_us-gaap_PublicUtilitiesInventoryAxis_019e6b08-e9fd-79d7-b14b-5271efa57faa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PublicUtilitiesInventoryTypeDomain_019e6b08-e9fd-79d7-b14b-5271efa57faa_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PublicUtilitiesInventoryTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PublicUtilitiesInventoryAxis_019e6b08-e9fd-79d7-b14b-5271efa57faa" xlink:to="loc_us-gaap_PublicUtilitiesInventoryTypeDomain_019e6b08-e9fd-79d7-b14b-5271efa57faa_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PublicUtilitiesInventoryTypeDomain_019e6b08-e9fd-7549-acac-b164015a0bcc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PublicUtilitiesInventoryTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PublicUtilitiesInventoryAxis_019e6b08-e9fd-79d7-b14b-5271efa57faa" xlink:to="loc_us-gaap_PublicUtilitiesInventoryTypeDomain_019e6b08-e9fd-7549-acac-b164015a0bcc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_InventoryHeldAtHospitalsAndTreatmentCentersMember_019e6b08-e9fd-7c2a-8efb-d42079ea06bf" xlink:href="dcth-20260630.xsd#dcth_InventoryHeldAtHospitalsAndTreatmentCentersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PublicUtilitiesInventoryTypeDomain_019e6b08-e9fd-7549-acac-b164015a0bcc" xlink:to="loc_dcth_InventoryHeldAtHospitalsAndTreatmentCentersMember_019e6b08-e9fd-7c2a-8efb-d42079ea06bf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryFinishedGoods_019e6b08-e9fd-73df-a760-4af904258ee6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InventoryFinishedGoods"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InventoryLineItems_019e6b08-e9fd-717e-8a2c-8c10d1811dc8" xlink:to="loc_us-gaap_InventoryFinishedGoods_019e6b08-e9fd-73df-a760-4af904258ee6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryValuationReserves_019e6b08-e9fd-7030-a93d-901bb934ac01" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InventoryValuationReserves"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InventoryLineItems_019e6b08-e9fd-717e-8a2c-8c10d1811dc8" xlink:to="loc_us-gaap_InventoryValuationReserves_019e6b08-e9fd-7030-a93d-901bb934ac01" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/PropertyPlantandEquipmentScheduleofPropertyPlantandEquipmentDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#PropertyPlantandEquipmentScheduleofPropertyPlantandEquipmentDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/PropertyPlantandEquipmentScheduleofPropertyPlantandEquipmentDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e6b08-e9fd-7d0b-aa5d-f18596e0d83f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_019e6b08-e9fd-7cb5-adfc-12bcdd4da028" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e6b08-e9fd-7d0b-aa5d-f18596e0d83f" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_019e6b08-e9fd-7cb5-adfc-12bcdd4da028" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e6b08-e9fd-7fff-890a-5d6b7e199266" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_019e6b08-e9fd-7cb5-adfc-12bcdd4da028" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e6b08-e9fd-7fff-890a-5d6b7e199266" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e6b08-e9fd-7fff-890a-5d6b7e199266_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e6b08-e9fd-7fff-890a-5d6b7e199266" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e6b08-e9fd-7fff-890a-5d6b7e199266_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e6b08-e9fd-7d2c-a08c-41e36b2ddd46" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e6b08-e9fd-7fff-890a-5d6b7e199266" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e6b08-e9fd-7d2c-a08c-41e36b2ddd46" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LandBuildingsAndImprovementsMember_019e6b08-e9fd-7ba2-aab4-1c757093c7c1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LandBuildingsAndImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e6b08-e9fd-7d2c-a08c-41e36b2ddd46" xlink:to="loc_us-gaap_LandBuildingsAndImprovementsMember_019e6b08-e9fd-7ba2-aab4-1c757093c7c1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BuildingMember_019e6b08-e9fd-794c-bd0e-001567ee8a8b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BuildingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LandBuildingsAndImprovementsMember_019e6b08-e9fd-7ba2-aab4-1c757093c7c1" xlink:to="loc_us-gaap_BuildingMember_019e6b08-e9fd-794c-bd0e-001567ee8a8b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LandAndLandImprovementsMember_019e6b08-e9fd-74fc-ae21-be37c1c4be04" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LandAndLandImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LandBuildingsAndImprovementsMember_019e6b08-e9fd-7ba2-aab4-1c757093c7c1" xlink:to="loc_us-gaap_LandAndLandImprovementsMember_019e6b08-e9fd-74fc-ae21-be37c1c4be04" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComputerEquipmentMember_019e6b08-e9fd-7ea6-89c2-4e391580a188" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ComputerEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e6b08-e9fd-7d2c-a08c-41e36b2ddd46" xlink:to="loc_us-gaap_ComputerEquipmentMember_019e6b08-e9fd-7ea6-89c2-4e391580a188" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseholdsAndLeaseholdImprovementsMember_019e6b08-e9fd-73b3-9f29-77ca6334a1fc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LeaseholdsAndLeaseholdImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e6b08-e9fd-7d2c-a08c-41e36b2ddd46" xlink:to="loc_us-gaap_LeaseholdsAndLeaseholdImprovementsMember_019e6b08-e9fd-73b3-9f29-77ca6334a1fc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquipmentMember_019e6b08-e9fd-7abb-954a-a7ac03961380" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e6b08-e9fd-7d2c-a08c-41e36b2ddd46" xlink:to="loc_us-gaap_EquipmentMember_019e6b08-e9fd-7abb-954a-a7ac03961380" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_019e6b08-e9fd-7fcb-ac7b-b865a13df958" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FurnitureAndFixturesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e6b08-e9fd-7d2c-a08c-41e36b2ddd46" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_019e6b08-e9fd-7fcb-ac7b-b865a13df958" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_EquipmentInProcessMember_019e6b08-e9fd-7fe0-ae27-d7a523a7ed83" xlink:href="dcth-20260630.xsd#dcth_EquipmentInProcessMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e6b08-e9fd-7d2c-a08c-41e36b2ddd46" xlink:to="loc_dcth_EquipmentInProcessMember_019e6b08-e9fd-7fe0-ae27-d7a523a7ed83" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_019e6b08-e9fd-774c-95be-52218e34c4d8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e6b08-e9fd-7d0b-aa5d-f18596e0d83f" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_019e6b08-e9fd-774c-95be-52218e34c4d8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_019e6b08-e9fd-704c-9df8-d1eddfea6c8a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e6b08-e9fd-7d0b-aa5d-f18596e0d83f" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_019e6b08-e9fd-704c-9df8-d1eddfea6c8a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_019e6b08-e9fd-7018-957c-c3d537bb49a4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e6b08-e9fd-7d0b-aa5d-f18596e0d83f" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_019e6b08-e9fd-7018-957c-c3d537bb49a4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_019e6b08-e9fd-715a-85ae-c8900f7135f2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e6b08-e9fd-7d0b-aa5d-f18596e0d83f" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_019e6b08-e9fd-715a-85ae-c8900f7135f2" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/LeasesNarrativeDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#LeasesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/LeasesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7dc4-b366-ff4998eea051" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeLeaseDescriptionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionTable_019e6b08-e9fd-742e-b6fa-4e64c7c01994" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeLeaseDescriptionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7dc4-b366-ff4998eea051" xlink:to="loc_us-gaap_LesseeLeaseDescriptionTable_019e6b08-e9fd-742e-b6fa-4e64c7c01994" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_LeaseArrangementAxis_019e6b08-e9fd-7a66-bc3b-c61c8f08dba7" xlink:href="dcth-20260630.xsd#dcth_LeaseArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_019e6b08-e9fd-742e-b6fa-4e64c7c01994" xlink:to="loc_dcth_LeaseArrangementAxis_019e6b08-e9fd-7a66-bc3b-c61c8f08dba7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_LeaseArrangementDomain_019e6b08-e9fd-7a66-bc3b-c61c8f08dba7_default" xlink:href="dcth-20260630.xsd#dcth_LeaseArrangementDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dcth_LeaseArrangementAxis_019e6b08-e9fd-7a66-bc3b-c61c8f08dba7" xlink:to="loc_dcth_LeaseArrangementDomain_019e6b08-e9fd-7a66-bc3b-c61c8f08dba7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_LeaseArrangementDomain_019e6b08-e9fd-737f-8249-b11d1ca6d808" xlink:href="dcth-20260630.xsd#dcth_LeaseArrangementDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dcth_LeaseArrangementAxis_019e6b08-e9fd-7a66-bc3b-c61c8f08dba7" xlink:to="loc_dcth_LeaseArrangementDomain_019e6b08-e9fd-737f-8249-b11d1ca6d808" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_SubLease2021Member_019e6b08-e9fd-73e3-9a58-51f5f25e3c28" xlink:href="dcth-20260630.xsd#dcth_SubLease2021Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_LeaseArrangementDomain_019e6b08-e9fd-737f-8249-b11d1ca6d808" xlink:to="loc_dcth_SubLease2021Member_019e6b08-e9fd-73e3-9a58-51f5f25e3c28" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_GalwayLeaseMember_019f40f8-71cf-7f3a-b581-f17cd9cd6ae1" xlink:href="dcth-20260630.xsd#dcth_GalwayLeaseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_LeaseArrangementDomain_019e6b08-e9fd-737f-8249-b11d1ca6d808" xlink:to="loc_dcth_GalwayLeaseMember_019f40f8-71cf-7f3a-b581-f17cd9cd6ae1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_QueensburyLeaseMember_019e6b08-e9fd-79c5-b1b1-14d3ceca59ec" xlink:href="dcth-20260630.xsd#dcth_QueensburyLeaseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_LeaseArrangementDomain_019e6b08-e9fd-737f-8249-b11d1ca6d808" xlink:to="loc_dcth_QueensburyLeaseMember_019e6b08-e9fd-79c5-b1b1-14d3ceca59ec" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseExpense_019e6b08-e9fd-736f-a01e-06dc4b2ad528" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7dc4-b366-ff4998eea051" xlink:to="loc_us-gaap_OperatingLeaseExpense_019e6b08-e9fd-736f-a01e-06dc4b2ad528" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermLeaseCost_019f69bf-5dc7-726e-83ad-3511263352c3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShortTermLeaseCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7dc4-b366-ff4998eea051" xlink:to="loc_us-gaap_ShortTermLeaseCost_019f69bf-5dc7-726e-83ad-3511263352c3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_LesseeOperatingLeaseContractualAnnualRentExpense_019e6b08-e9fd-7abe-8399-8afdfb5641f8" xlink:href="dcth-20260630.xsd#dcth_LesseeOperatingLeaseContractualAnnualRentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7dc4-b366-ff4998eea051" xlink:to="loc_dcth_LesseeOperatingLeaseContractualAnnualRentExpense_019e6b08-e9fd-7abe-8399-8afdfb5641f8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseTermOfContract_019e6b08-e9fd-773f-9db6-d6d0a7b27037" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseTermOfContract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7dc4-b366-ff4998eea051" xlink:to="loc_us-gaap_LesseeOperatingLeaseTermOfContract_019e6b08-e9fd-773f-9db6-d6d0a7b27037" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AreaOfRealEstateProperty_019e6b08-e9fd-7feb-bbe4-cc5a2a2e5283" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AreaOfRealEstateProperty"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7dc4-b366-ff4998eea051" xlink:to="loc_us-gaap_AreaOfRealEstateProperty_019e6b08-e9fd-7feb-bbe4-cc5a2a2e5283" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_019e6b08-e9fd-7237-a363-20ebd0757860" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7dc4-b366-ff4998eea051" xlink:to="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_019e6b08-e9fd-7237-a363-20ebd0757860" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/LeasesScheduleofOperatingLeasesDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#LeasesScheduleofOperatingLeasesDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/LeasesScheduleofOperatingLeasesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7034-88e0-4df35581dead" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeLeaseDescriptionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionTable_019e6b08-e9fd-7731-a4dd-32b00bd29908" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeLeaseDescriptionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7034-88e0-4df35581dead" xlink:to="loc_us-gaap_LesseeLeaseDescriptionTable_019e6b08-e9fd-7731-a4dd-32b00bd29908" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_019e6b08-e9fd-7db6-832f-7c9e09d39704" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_019e6b08-e9fd-7731-a4dd-32b00bd29908" xlink:to="loc_srt_StatementGeographicalAxis_019e6b08-e9fd-7db6-832f-7c9e09d39704" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-7db6-832f-7c9e09d39704_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_019e6b08-e9fd-7db6-832f-7c9e09d39704" xlink:to="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-7db6-832f-7c9e09d39704_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-7f6a-b54b-0d65c0e4f29f" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_019e6b08-e9fd-7db6-832f-7c9e09d39704" xlink:to="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-7f6a-b54b-0d65c0e4f29f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_country_US_019e6b08-e9fd-7580-9eee-e1b3f0b3b4fc" xlink:href="https://xbrl.sec.gov/country/2026/country-2026.xsd#country_US"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-7f6a-b54b-0d65c0e4f29f" xlink:to="loc_country_US_019e6b08-e9fd-7580-9eee-e1b3f0b3b4fc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_country_IE_019e6b08-e9fd-74f3-ba22-72528ac3ddf2" xlink:href="https://xbrl.sec.gov/country/2026/country-2026.xsd#country_IE"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-7f6a-b54b-0d65c0e4f29f" xlink:to="loc_country_IE_019e6b08-e9fd-74f3-ba22-72528ac3ddf2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_OtherLeaseInformationAbstract_019e6b08-e9fd-7747-a9ae-6dae8a8909e2" xlink:href="dcth-20260630.xsd#dcth_OtherLeaseInformationAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7034-88e0-4df35581dead" xlink:to="loc_dcth_OtherLeaseInformationAbstract_019e6b08-e9fd-7747-a9ae-6dae8a8909e2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeasePayments_019e6b08-e9fd-7df6-a092-4befc81a541a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeasePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_OtherLeaseInformationAbstract_019e6b08-e9fd-7747-a9ae-6dae8a8909e2" xlink:to="loc_us-gaap_OperatingLeasePayments_019e6b08-e9fd-7df6-a092-4befc81a541a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_019e6b08-e9fd-7919-a54f-2d14c16fd685" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_OtherLeaseInformationAbstract_019e6b08-e9fd-7747-a9ae-6dae8a8909e2" xlink:to="loc_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_019e6b08-e9fd-7919-a54f-2d14c16fd685" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_019e6b08-e9fd-7c95-b4b7-8ee281cd77a8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_OtherLeaseInformationAbstract_019e6b08-e9fd-7747-a9ae-6dae8a8909e2" xlink:to="loc_us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_019e6b08-e9fd-7c95-b4b7-8ee281cd77a8" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/LeasesScheduleofRemainingMaturityofOperatingLeasesExcludingShorttermLeasesDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#LeasesScheduleofRemainingMaturityofOperatingLeasesExcludingShorttermLeasesDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/LeasesScheduleofRemainingMaturityofOperatingLeasesExcludingShorttermLeasesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7c21-ac02-f8d31f4b8165" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeLeaseDescriptionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionTable_019e6b08-e9fd-7b6f-b784-e74cff54602e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeLeaseDescriptionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7c21-ac02-f8d31f4b8165" xlink:to="loc_us-gaap_LesseeLeaseDescriptionTable_019e6b08-e9fd-7b6f-b784-e74cff54602e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_019e6b08-e9fd-7bef-8351-8137e9118246" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_019e6b08-e9fd-7b6f-b784-e74cff54602e" xlink:to="loc_srt_StatementGeographicalAxis_019e6b08-e9fd-7bef-8351-8137e9118246" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-7bef-8351-8137e9118246_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_019e6b08-e9fd-7bef-8351-8137e9118246" xlink:to="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-7bef-8351-8137e9118246_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-79c0-bfc1-2451e48180a2" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_019e6b08-e9fd-7bef-8351-8137e9118246" xlink:to="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-79c0-bfc1-2451e48180a2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_country_US_019e6b08-e9fd-7a57-8ce2-e10fbd81cd3d" xlink:href="https://xbrl.sec.gov/country/2026/country-2026.xsd#country_US"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-79c0-bfc1-2451e48180a2" xlink:to="loc_country_US_019e6b08-e9fd-7a57-8ce2-e10fbd81cd3d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_country_IE_019e6b08-e9fd-7fa0-beeb-2b9d8c7bf112" xlink:href="https://xbrl.sec.gov/country/2026/country-2026.xsd#country_IE"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019e6b08-e9fd-79c0-bfc1-2451e48180a2" xlink:to="loc_country_IE_019e6b08-e9fd-7fa0-beeb-2b9d8c7bf112" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear_019e6b08-e9fd-7dd6-b155-1fee18be7808" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7c21-ac02-f8d31f4b8165" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsRemainderOfFiscalYear_019e6b08-e9fd-7dd6-b155-1fee18be7808" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_019e6b08-e9fd-7325-a875-d3c8bcbb4427" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7c21-ac02-f8d31f4b8165" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_019e6b08-e9fd-7325-a875-d3c8bcbb4427" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_019e6b08-e9fd-7f96-85e8-16ef6451b112" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7c21-ac02-f8d31f4b8165" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_019e6b08-e9fd-7f96-85e8-16ef6451b112" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_019e6b08-e9fd-7f07-8b9f-aed561b57646" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7c21-ac02-f8d31f4b8165" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_019e6b08-e9fd-7f07-8b9f-aed561b57646" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_019e6b08-e9fd-7e1c-90c9-053a11354630" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7c21-ac02-f8d31f4b8165" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_019e6b08-e9fd-7e1c-90c9-053a11354630" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_LesseeOperatingLeaseLiabilityToBePaidDueAfterYearFour_019e6b08-e9fd-72a7-99f1-8bca4d806765" xlink:href="dcth-20260630.xsd#dcth_LesseeOperatingLeaseLiabilityToBePaidDueAfterYearFour"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7c21-ac02-f8d31f4b8165" xlink:to="loc_dcth_LesseeOperatingLeaseLiabilityToBePaidDueAfterYearFour_019e6b08-e9fd-72a7-99f1-8bca4d806765" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019e6b08-e9fd-75cf-a4c1-0b5ee4bec571" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7c21-ac02-f8d31f4b8165" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019e6b08-e9fd-75cf-a4c1-0b5ee4bec571" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_019e6b08-e9fd-77ac-b1a2-80ddbf671ef4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7c21-ac02-f8d31f4b8165" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_019e6b08-e9fd-77ac-b1a2-80ddbf671ef4" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiability_019e6b08-e9fd-7725-9783-3265c7fc9068" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e6b08-e9fd-7c21-ac02-f8d31f4b8165" xlink:to="loc_us-gaap_OperatingLeaseLiability_019e6b08-e9fd-7725-9783-3265c7fc9068" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/StockholdersEquityPublicandPrivatePlacementsDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#StockholdersEquityPublicandPrivatePlacementsDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/StockholdersEquityPublicandPrivatePlacementsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_dcth_StockholdersEquityNoteLineItems_019e6b08-e9fd-7995-b180-243374fd7eb5" xlink:href="dcth-20260630.xsd#dcth_StockholdersEquityNoteLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_StockholdersEquityNoteTable_019e6b08-e9fd-75f9-8c23-5e52da410d66" xlink:href="dcth-20260630.xsd#dcth_StockholdersEquityNoteTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_dcth_StockholdersEquityNoteLineItems_019e6b08-e9fd-7995-b180-243374fd7eb5" xlink:to="loc_dcth_StockholdersEquityNoteTable_019e6b08-e9fd-75f9-8c23-5e52da410d66" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_019e6b08-e9fd-76f8-b690-e0fe81ff0648" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_dcth_StockholdersEquityNoteTable_019e6b08-e9fd-75f9-8c23-5e52da410d66" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_019e6b08-e9fd-76f8-b690-e0fe81ff0648" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019e6b08-e9fd-76f8-b690-e0fe81ff0648_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_019e6b08-e9fd-76f8-b690-e0fe81ff0648" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019e6b08-e9fd-76f8-b690-e0fe81ff0648_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019e6b08-e9fd-7d76-a18c-ff1c1e8674b9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_019e6b08-e9fd-76f8-b690-e0fe81ff0648" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019e6b08-e9fd-7d76-a18c-ff1c1e8674b9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_June2024ShelfRegistrationStatementMember_019e6b08-e9fd-72b4-833f-7aff2734a259" xlink:href="dcth-20260630.xsd#dcth_June2024ShelfRegistrationStatementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019e6b08-e9fd-7d76-a18c-ff1c1e8674b9" xlink:to="loc_dcth_June2024ShelfRegistrationStatementMember_019e6b08-e9fd-72b4-833f-7aff2734a259" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_019e6b08-e9fd-77ed-a9bb-61c85c03b65a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_StockholdersEquityNoteLineItems_019e6b08-e9fd-7995-b180-243374fd7eb5" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_019e6b08-e9fd-77ed-a9bb-61c85c03b65a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019e6b08-e9fd-78ea-93a3-284a2d34ac3c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_StockholdersEquityNoteLineItems_019e6b08-e9fd-7995-b180-243374fd7eb5" xlink:to="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019e6b08-e9fd-78ea-93a3-284a2d34ac3c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_MaximumAggregateOfferingPriceOfSecuritiesUnderShelfRegistration_019e6b08-e9fd-7df8-9123-e6ca2ecf53ad" xlink:href="dcth-20260630.xsd#dcth_MaximumAggregateOfferingPriceOfSecuritiesUnderShelfRegistration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_StockholdersEquityNoteLineItems_019e6b08-e9fd-7995-b180-243374fd7eb5" xlink:to="loc_dcth_MaximumAggregateOfferingPriceOfSecuritiesUnderShelfRegistration_019e6b08-e9fd-7df8-9123-e6ca2ecf53ad" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/StockholdersEquityScheduleofDesignatedPreferredSharesDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#StockholdersEquityScheduleofDesignatedPreferredSharesDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/StockholdersEquityScheduleofDesignatedPreferredSharesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_019e6b08-e9fd-72b9-8462-845b96716dd4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_019e6b08-e9fd-7746-878b-0db8945d2b85" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_019e6b08-e9fd-72b9-8462-845b96716dd4" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_019e6b08-e9fd-7746-878b-0db8945d2b85" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-728e-b9d6-940dac21d0b3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_019e6b08-e9fd-7746-878b-0db8945d2b85" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-728e-b9d6-940dac21d0b3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-728e-b9d6-940dac21d0b3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-728e-b9d6-940dac21d0b3" xlink:to="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-728e-b9d6-940dac21d0b3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-728e-b9d6-940dac21d0b3" xlink:to="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesAPreferredStockMember_019e6b08-e9fd-724b-88e4-3236599ec1a6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeriesAPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:to="loc_us-gaap_SeriesAPreferredStockMember_019e6b08-e9fd-724b-88e4-3236599ec1a6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesBPreferredStockMember_019e6b08-e9fd-7e45-8d5b-8f9f7e814a9b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeriesBPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:to="loc_us-gaap_SeriesBPreferredStockMember_019e6b08-e9fd-7e45-8d5b-8f9f7e814a9b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesCPreferredStockMember_019e6b08-e9fd-79aa-8336-86eb43311b73" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeriesCPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:to="loc_us-gaap_SeriesCPreferredStockMember_019e6b08-e9fd-79aa-8336-86eb43311b73" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesDPreferredStockMember_019e6b08-e9fd-755c-a306-7285c5d7e490" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeriesDPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:to="loc_us-gaap_SeriesDPreferredStockMember_019e6b08-e9fd-755c-a306-7285c5d7e490" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesEPreferredStockMember_019e6b08-e9fd-73e0-8aff-b0343b13d3df" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeriesEPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:to="loc_us-gaap_SeriesEPreferredStockMember_019e6b08-e9fd-73e0-8aff-b0343b13d3df" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_SeriesE1PreferredStockMember_019e6b08-e9fd-7706-a4a7-65df19389074" xlink:href="dcth-20260630.xsd#dcth_SeriesE1PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:to="loc_dcth_SeriesE1PreferredStockMember_019e6b08-e9fd-7706-a4a7-65df19389074" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_SeriesF1PreferredStockMember_019e6b08-e9fd-72d4-8205-9974e8344620" xlink:href="dcth-20260630.xsd#dcth_SeriesF1PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:to="loc_dcth_SeriesF1PreferredStockMember_019e6b08-e9fd-72d4-8205-9974e8344620" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_SeriesF2PreferredStockMember_019e6b08-e9fd-7955-a4d2-924c66da159b" xlink:href="dcth-20260630.xsd#dcth_SeriesF2PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:to="loc_dcth_SeriesF2PreferredStockMember_019e6b08-e9fd-7955-a4d2-924c66da159b" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_SeriesF3PreferredStockMember_019e6b08-e9fd-7383-a057-42be6d97a8b3" xlink:href="dcth-20260630.xsd#dcth_SeriesF3PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:to="loc_dcth_SeriesF3PreferredStockMember_019e6b08-e9fd-7383-a057-42be6d97a8b3" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_SeriesF4PreferredStockMember_019e6b08-e9fd-7e00-8837-c71ed07696c9" xlink:href="dcth-20260630.xsd#dcth_SeriesF4PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7803-b621-d0c721f28e7e" xlink:to="loc_dcth_SeriesF4PreferredStockMember_019e6b08-e9fd-7e00-8837-c71ed07696c9" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_PreferredStockSharesDesignated_019e6b08-e9fd-7df1-ab92-d5f93471c1f4" xlink:href="dcth-20260630.xsd#dcth_PreferredStockSharesDesignated"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_019e6b08-e9fd-72b9-8462-845b96716dd4" xlink:to="loc_dcth_PreferredStockSharesDesignated_019e6b08-e9fd-7df1-ab92-d5f93471c1f4" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/StockholdersEquityPreferredStockDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#StockholdersEquityPreferredStockDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/StockholdersEquityPreferredStockDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-e9fd-7485-9e5a-55d9955a6197" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-e9fd-70e7-8ece-9f7b3f0aa5bc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-e9fd-7485-9e5a-55d9955a6197" xlink:to="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-e9fd-70e7-8ece-9f7b3f0aa5bc" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-7cb8-88ca-8ac543bffc9d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-e9fd-70e7-8ece-9f7b3f0aa5bc" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-7cb8-88ca-8ac543bffc9d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7cb8-88ca-8ac543bffc9d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-7cb8-88ca-8ac543bffc9d" xlink:to="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7cb8-88ca-8ac543bffc9d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7456-913f-1cb78fef2216" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e6b08-e9fd-7cb8-88ca-8ac543bffc9d" xlink:to="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7456-913f-1cb78fef2216" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_SeriesE1PreferredStockMember_019e6b08-e9fd-7377-b268-65390681d122" xlink:href="dcth-20260630.xsd#dcth_SeriesE1PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7456-913f-1cb78fef2216" xlink:to="loc_dcth_SeriesE1PreferredStockMember_019e6b08-e9fd-7377-b268-65390681d122" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesEPreferredStockMember_019e6b08-e9fd-7f60-8352-a3bb9f98fb12" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeriesEPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7456-913f-1cb78fef2216" xlink:to="loc_us-gaap_SeriesEPreferredStockMember_019e6b08-e9fd-7f60-8352-a3bb9f98fb12" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_SeriesF2PreferredStockMember_019e6b08-e9fd-7303-ba72-1c6c8d614f4f" xlink:href="dcth-20260630.xsd#dcth_SeriesF2PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7456-913f-1cb78fef2216" xlink:to="loc_dcth_SeriesF2PreferredStockMember_019e6b08-e9fd-7303-ba72-1c6c8d614f4f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_SeriesF4PreferredStockMember_019e6b08-e9fd-7239-bcd1-2d14edcbdfc2" xlink:href="dcth-20260630.xsd#dcth_SeriesF4PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e6b08-e9fd-7456-913f-1cb78fef2216" xlink:to="loc_dcth_SeriesF4PreferredStockMember_019e6b08-e9fd-7239-bcd1-2d14edcbdfc2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesOutstanding_019e6b08-e9fd-7ca3-a3ff-9e3a275244d7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-e9fd-7485-9e5a-55d9955a6197" xlink:to="loc_us-gaap_PreferredStockSharesOutstanding_019e6b08-e9fd-7ca3-a3ff-9e3a275244d7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019e6b08-e9fd-7b5e-9fc1-9c330b298787" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-e9fd-7485-9e5a-55d9955a6197" xlink:to="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019e6b08-e9fd-7b5e-9fc1-9c330b298787" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/StockholdersEquityOmnibusEquityIncentivePlanDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#StockholdersEquityOmnibusEquityIncentivePlanDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/StockholdersEquityOmnibusEquityIncentivePlanDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-e9fd-7718-a48f-77fae4d7e0e9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-e9fd-76bb-ba9a-e370b690c65d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-e9fd-7718-a48f-77fae4d7e0e9" xlink:to="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-e9fd-76bb-ba9a-e370b690c65d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_019e6b08-e9fd-7086-aa76-57bc5db538c1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-e9fd-76bb-ba9a-e370b690c65d" xlink:to="loc_us-gaap_PlanNameAxis_019e6b08-e9fd-7086-aa76-57bc5db538c1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e6b08-e9fd-7086-aa76-57bc5db538c1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_019e6b08-e9fd-7086-aa76-57bc5db538c1" xlink:to="loc_us-gaap_PlanNameDomain_019e6b08-e9fd-7086-aa76-57bc5db538c1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e6b08-e9fd-7a5f-844e-f236f29a2e43" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_019e6b08-e9fd-7086-aa76-57bc5db538c1" xlink:to="loc_us-gaap_PlanNameDomain_019e6b08-e9fd-7a5f-844e-f236f29a2e43" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_A2020PlanMember_019e6b08-e9fd-77d4-90d1-56ca3e2c3c0f" xlink:href="dcth-20260630.xsd#dcth_A2020PlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019e6b08-e9fd-7a5f-844e-f236f29a2e43" xlink:to="loc_dcth_A2020PlanMember_019e6b08-e9fd-77d4-90d1-56ca3e2c3c0f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_A2023PlanMember_019e6b08-e9fd-71da-a762-7f690396fb8f" xlink:href="dcth-20260630.xsd#dcth_A2023PlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019e6b08-e9fd-7a5f-844e-f236f29a2e43" xlink:to="loc_dcth_A2023PlanMember_019e6b08-e9fd-71da-a762-7f690396fb8f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_019e6b08-e9fd-75f1-856a-e5ca7be2668e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-e9fd-7718-a48f-77fae4d7e0e9" xlink:to="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_019e6b08-e9fd-75f1-856a-e5ca7be2668e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_019ed9da-2f7d-79d0-91e4-3ffcef28e09d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-e9fd-7718-a48f-77fae4d7e0e9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_019ed9da-2f7d-79d0-91e4-3ffcef28e09d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_019e6b08-e9fd-70c6-8ef8-3f42b8c535d0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-e9fd-7718-a48f-77fae4d7e0e9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_019e6b08-e9fd-70c6-8ef8-3f42b8c535d0" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/StockholdersEquityScheduleofRestrictedStockUnitsActivityDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#StockholdersEquityScheduleofRestrictedStockUnitsActivityDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/StockholdersEquityScheduleofRestrictedStockUnitsActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_dcth_StockholdersEquityNoteLineItems_019e6b08-e9fe-7ac0-896a-75d782eff165" xlink:href="dcth-20260630.xsd#dcth_StockholdersEquityNoteLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_StockholdersEquityNoteTable_019e6b08-e9fe-7977-952c-989e4e5c35cf" xlink:href="dcth-20260630.xsd#dcth_StockholdersEquityNoteTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_dcth_StockholdersEquityNoteLineItems_019e6b08-e9fe-7ac0-896a-75d782eff165" xlink:to="loc_dcth_StockholdersEquityNoteTable_019e6b08-e9fe-7977-952c-989e4e5c35cf" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e6b08-e9fe-72a5-aa53-ee09f26f0eff" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_dcth_StockholdersEquityNoteTable_019e6b08-e9fe-7977-952c-989e4e5c35cf" xlink:to="loc_us-gaap_AwardTypeAxis_019e6b08-e9fe-72a5-aa53-ee09f26f0eff" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e6b08-e9fe-72a5-aa53-ee09f26f0eff_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e6b08-e9fe-72a5-aa53-ee09f26f0eff" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e6b08-e9fe-72a5-aa53-ee09f26f0eff_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e6b08-e9fe-7094-9603-1215dbfe157d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e6b08-e9fe-72a5-aa53-ee09f26f0eff" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e6b08-e9fe-7094-9603-1215dbfe157d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019e6b08-e9fe-712d-ae3c-b79ef92bc87c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e6b08-e9fe-7094-9603-1215dbfe157d" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019e6b08-e9fe-712d-ae3c-b79ef92bc87c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e6b08-e9fe-7e98-9eff-83ae700e4414" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_StockholdersEquityNoteLineItems_019e6b08-e9fe-7ac0-896a-75d782eff165" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e6b08-e9fe-7e98-9eff-83ae700e4414" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019e6b08-e9fe-72f4-bfeb-6b5c3243e0c6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e6b08-e9fe-7e98-9eff-83ae700e4414" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019e6b08-e9fe-72f4-bfeb-6b5c3243e0c6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019e6b08-e9fe-73c2-a711-e315d6cc9144" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e6b08-e9fe-7e98-9eff-83ae700e4414" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019e6b08-e9fe-73c2-a711-e315d6cc9144" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019e6b08-e9fe-7b07-abf2-7581c7ea4da2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e6b08-e9fe-7e98-9eff-83ae700e4414" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019e6b08-e9fe-7b07-abf2-7581c7ea4da2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_019e6b08-e9fe-73ec-a9a2-965c72fb128a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e6b08-e9fe-7e98-9eff-83ae700e4414" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_019e6b08-e9fe-73ec-a9a2-965c72fb128a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019e6b08-e9fe-74b1-9a72-480a1a1339e9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e6b08-e9fe-7b86-96be-b698af7064f3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_StockholdersEquityNoteLineItems_019e6b08-e9fe-7ac0-896a-75d782eff165" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e6b08-e9fe-7b86-96be-b698af7064f3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019e6b08-e9fe-78f2-ac4d-959493dc4836" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e6b08-e9fe-7b86-96be-b698af7064f3" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019e6b08-e9fe-78f2-ac4d-959493dc4836" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019e6b08-e9fe-7268-8c00-ea5aef34dc83" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e6b08-e9fe-7b86-96be-b698af7064f3" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019e6b08-e9fe-7268-8c00-ea5aef34dc83" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_019e6b08-e9fe-7b46-ab77-1ae301cb3429" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e6b08-e9fe-7b86-96be-b698af7064f3" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_019e6b08-e9fe-7b46-ab77-1ae301cb3429" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_019e6b08-eaf2-747d-b55a-0a0b9657d3f6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e6b08-e9fe-7b86-96be-b698af7064f3" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_019e6b08-eaf2-747d-b55a-0a0b9657d3f6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019e6b08-eaf2-7cac-b3aa-e814714a9d7d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/StockholdersEquityScheduleofRecognizedSharebasedCompensationCostDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#StockholdersEquityScheduleofRecognizedSharebasedCompensationCostDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/StockholdersEquityScheduleofRecognizedSharebasedCompensationCostDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019e6b08-eaf2-7f19-aea9-abd8ac5d8767" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019e6b08-eaf2-722a-ae74-d1c74689dfe2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019e6b08-eaf2-7f19-aea9-abd8ac5d8767" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019e6b08-eaf2-722a-ae74-d1c74689dfe2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_019e6b08-eaf2-75f5-a101-e534f59cf7fb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019e6b08-eaf2-722a-ae74-d1c74689dfe2" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_019e6b08-eaf2-75f5-a101-e534f59cf7fb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_019e6b08-eaf2-710f-bd84-f777540768ab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019e6b08-eaf2-7f19-aea9-abd8ac5d8767" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_019e6b08-eaf2-710f-bd84-f777540768ab" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/StockholdersEquityScheduleofRecognizedSharebasedCompensationCostDetails_1" xlink:type="simple" xlink:href="dcth-20260630.xsd#StockholdersEquityScheduleofRecognizedSharebasedCompensationCostDetails_1"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/StockholdersEquityScheduleofRecognizedSharebasedCompensationCostDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019e6b08-eaf2-7f19-aea9-abd8ac5d8767" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019e6b08-eaf2-722a-ae74-d1c74689dfe2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019e6b08-eaf2-7f19-aea9-abd8ac5d8767" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019e6b08-eaf2-722a-ae74-d1c74689dfe2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_019e6b08-eaf2-710f-bd84-f777540768ab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019e6b08-eaf2-7f19-aea9-abd8ac5d8767" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_019e6b08-eaf2-710f-bd84-f777540768ab" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/StockholdersEquityScheduleofWarrantActivityDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#StockholdersEquityScheduleofWarrantActivityDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/StockholdersEquityScheduleofWarrantActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-eaf2-7610-bf6c-1e93e102c673" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-eaf2-7883-9ee8-0932a875e290" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-eaf2-7610-bf6c-1e93e102c673" xlink:to="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-eaf2-7883-9ee8-0932a875e290" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_019e6b08-eaf2-7788-9927-694a62461398" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-eaf2-7883-9ee8-0932a875e290" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_019e6b08-eaf2-7788-9927-694a62461398" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_019e6b08-eaf2-7788-9927-694a62461398_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_019e6b08-eaf2-7788-9927-694a62461398" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_019e6b08-eaf2-7788-9927-694a62461398_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_019e6b08-eaf2-7b25-906b-5aa7e6c28215" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_019e6b08-eaf2-7788-9927-694a62461398" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_019e6b08-eaf2-7b25-906b-5aa7e6c28215" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_CommonWarrantsMember_019e6b08-eaf2-7ec0-941a-9c6d79fa6018" xlink:href="dcth-20260630.xsd#dcth_CommonWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_019e6b08-eaf2-7b25-906b-5aa7e6c28215" xlink:to="loc_dcth_CommonWarrantsMember_019e6b08-eaf2-7ec0-941a-9c6d79fa6018" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClassOfWarrantOrRightOutstandingRollForward_019e6b08-eaf2-7702-b844-69126a012c27" xlink:href="dcth-20260630.xsd#dcth_ClassOfWarrantOrRightOutstandingRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-eaf2-7610-bf6c-1e93e102c673" xlink:to="loc_dcth_ClassOfWarrantOrRightOutstandingRollForward_019e6b08-eaf2-7702-b844-69126a012c27" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightOutstanding_019e6b08-eaf2-7740-b5fb-c90b7e5795e6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_ClassOfWarrantOrRightOutstandingRollForward_019e6b08-eaf2-7702-b844-69126a012c27" xlink:to="loc_us-gaap_ClassOfWarrantOrRightOutstanding_019e6b08-eaf2-7740-b5fb-c90b7e5795e6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClassOfWarrantOrRightIssued_019e6b08-eaf2-71a7-b31c-907234668354" xlink:href="dcth-20260630.xsd#dcth_ClassOfWarrantOrRightIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_ClassOfWarrantOrRightOutstandingRollForward_019e6b08-eaf2-7702-b844-69126a012c27" xlink:to="loc_dcth_ClassOfWarrantOrRightIssued_019e6b08-eaf2-71a7-b31c-907234668354" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClassOfWarrantOrRightExercised_019e6b08-eaf2-7df0-aa18-d44adac1d2d7" xlink:href="dcth-20260630.xsd#dcth_ClassOfWarrantOrRightExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_ClassOfWarrantOrRightOutstandingRollForward_019e6b08-eaf2-7702-b844-69126a012c27" xlink:to="loc_dcth_ClassOfWarrantOrRightExercised_019e6b08-eaf2-7df0-aa18-d44adac1d2d7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClassOfWarrantOrRightCancelled_019e6b08-eaf2-7429-9dac-a39fc60eb1e8" xlink:href="dcth-20260630.xsd#dcth_ClassOfWarrantOrRightCancelled"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_ClassOfWarrantOrRightOutstandingRollForward_019e6b08-eaf2-7702-b844-69126a012c27" xlink:to="loc_dcth_ClassOfWarrantOrRightCancelled_019e6b08-eaf2-7429-9dac-a39fc60eb1e8" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightOutstanding_019e6b08-eaf2-7455-ba84-54d09943e358" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceAbstract_019e6b08-eaf2-79a3-aca7-bc0f491ecf0c" xlink:href="dcth-20260630.xsd#dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-eaf2-7610-bf6c-1e93e102c673" xlink:to="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceAbstract_019e6b08-eaf2-79a3-aca7-bc0f491ecf0c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePrice_019e6b08-eaf2-7bb2-a537-513c0d52abfb" xlink:href="dcth-20260630.xsd#dcth_ClassOfWarrantOrRightWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceAbstract_019e6b08-eaf2-79a3-aca7-bc0f491ecf0c" xlink:to="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePrice_019e6b08-eaf2-7bb2-a537-513c0d52abfb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceIssued_019e6b08-eaf2-7de9-854b-da297cd04370" xlink:href="dcth-20260630.xsd#dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceAbstract_019e6b08-eaf2-79a3-aca7-bc0f491ecf0c" xlink:to="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceIssued_019e6b08-eaf2-7de9-854b-da297cd04370" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceExercised_019e6b08-eaf2-7073-8c9c-2eccb62ebd3e" xlink:href="dcth-20260630.xsd#dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceAbstract_019e6b08-eaf2-79a3-aca7-bc0f491ecf0c" xlink:to="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceExercised_019e6b08-eaf2-7073-8c9c-2eccb62ebd3e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceCancelled_019e6b08-eaf2-783b-b1b0-b5518ce1df26" xlink:href="dcth-20260630.xsd#dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceCancelled"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceAbstract_019e6b08-eaf2-79a3-aca7-bc0f491ecf0c" xlink:to="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePriceCancelled_019e6b08-eaf2-783b-b1b0-b5518ce1df26" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ClassOfWarrantOrRightWeightedAverageExercisePrice_019e6b08-eaf2-73c4-b09c-e450fbe5e986" xlink:href="dcth-20260630.xsd#dcth_ClassOfWarrantOrRightWeightedAverageExercisePrice"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/StockholdersEquityScheduleofInformationRelatedtoStockWarrantsOutstandingandExercisableDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#StockholdersEquityScheduleofInformationRelatedtoStockWarrantsOutstandingandExercisableDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/StockholdersEquityScheduleofInformationRelatedtoStockWarrantsOutstandingandExercisableDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-eaf2-7d3c-a2d3-824d154497bc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-eaf2-7e52-b26d-49e2b35357d9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-eaf2-7d3c-a2d3-824d154497bc" xlink:to="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-eaf2-7e52-b26d-49e2b35357d9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_019e6b08-eaf2-7095-9257-6021d1f84429" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-eaf2-7e52-b26d-49e2b35357d9" xlink:to="loc_us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_019e6b08-eaf2-7095-9257-6021d1f84429" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_019e6b08-eaf2-7095-9257-6021d1f84429_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_019e6b08-eaf2-7095-9257-6021d1f84429" xlink:to="loc_us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_019e6b08-eaf2-7095-9257-6021d1f84429_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_019e6b08-eaf2-722d-a64c-f80404a22414" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansByExercisePriceRangeAxis_019e6b08-eaf2-7095-9257-6021d1f84429" xlink:to="loc_us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_019e6b08-eaf2-722d-a64c-f80404a22414" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ExercisePriceRangeOneMember_019e6b08-eaf2-7d57-afc3-7c8c7d4c87f4" xlink:href="dcth-20260630.xsd#dcth_ExercisePriceRangeOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationSharesAuthorizedUnderStockOptionPlansExercisePriceRangeDomain_019e6b08-eaf2-722d-a64c-f80404a22414" xlink:to="loc_dcth_ExercisePriceRangeOneMember_019e6b08-eaf2-7d57-afc3-7c8c7d4c87f4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_019e6b08-eaf2-7638-bbd2-211b443f0b0b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ClassOfWarrantOrRightTable_019e6b08-eaf2-7e52-b26d-49e2b35357d9" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_019e6b08-eaf2-7638-bbd2-211b443f0b0b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_019e6b08-eaf2-7638-bbd2-211b443f0b0b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_019e6b08-eaf2-7638-bbd2-211b443f0b0b" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_019e6b08-eaf2-7638-bbd2-211b443f0b0b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_019e6b08-eaf2-7310-b9c4-041e8fb8b81e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_019e6b08-eaf2-7638-bbd2-211b443f0b0b" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_019e6b08-eaf2-7310-b9c4-041e8fb8b81e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_CommonWarrantsMember_019e6b08-eaf2-71a5-ab27-9954b776a064" xlink:href="dcth-20260630.xsd#dcth_CommonWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_019e6b08-eaf2-7310-b9c4-041e8fb8b81e" xlink:to="loc_dcth_CommonWarrantsMember_019e6b08-eaf2-71a5-ab27-9954b776a064" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_019e6b08-eaf2-7726-80ea-d50d8dab5560" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-eaf2-7d3c-a2d3-824d154497bc" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_019e6b08-eaf2-7726-80ea-d50d8dab5560" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightOutstanding_019e6b08-eaf2-7ed9-8ee7-748e683bf693" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e6b08-eaf2-7d3c-a2d3-824d154497bc" xlink:to="loc_us-gaap_ClassOfWarrantOrRightOutstanding_019e6b08-eaf2-7ed9-8ee7-748e683bf693" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/StockholdersEquityEmployeeStockPurchasePlanDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#StockholdersEquityEmployeeStockPurchasePlanDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/StockholdersEquityEmployeeStockPurchasePlanDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOwnershipPlanESOPDisclosuresLineItems_019e6b08-eaf2-74c9-8a5e-51bdfaa35afe" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeStockOwnershipPlanESOPDisclosuresLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeStockOwnershipPlanESOPDisclosuresTable_019e6b08-eaf2-7af5-a12b-147203a94ae1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfEmployeeStockOwnershipPlanESOPDisclosuresTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeStockOwnershipPlanESOPDisclosuresLineItems_019e6b08-eaf2-74c9-8a5e-51bdfaa35afe" xlink:to="loc_us-gaap_ScheduleOfEmployeeStockOwnershipPlanESOPDisclosuresTable_019e6b08-eaf2-7af5-a12b-147203a94ae1" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_019e6b08-eaf2-7521-ab39-43059747b0b1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeStockOwnershipPlanESOPDisclosuresTable_019e6b08-eaf2-7af5-a12b-147203a94ae1" xlink:to="loc_us-gaap_PlanNameAxis_019e6b08-eaf2-7521-ab39-43059747b0b1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e6b08-eaf2-7521-ab39-43059747b0b1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_019e6b08-eaf2-7521-ab39-43059747b0b1" xlink:to="loc_us-gaap_PlanNameDomain_019e6b08-eaf2-7521-ab39-43059747b0b1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e6b08-eaf2-7c70-a73a-18b1bbd1080a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_019e6b08-eaf2-7521-ab39-43059747b0b1" xlink:to="loc_us-gaap_PlanNameDomain_019e6b08-eaf2-7c70-a73a-18b1bbd1080a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_MayTwoThousandAndTwentyTwoEmployeeStockPurchasePlanMember_019e6b08-eaf2-7f76-8916-39556bd615ce" xlink:href="dcth-20260630.xsd#dcth_MayTwoThousandAndTwentyTwoEmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019e6b08-eaf2-7c70-a73a-18b1bbd1080a" xlink:to="loc_dcth_MayTwoThousandAndTwentyTwoEmployeeStockPurchasePlanMember_019e6b08-eaf2-7f76-8916-39556bd615ce" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_019e6b08-eaf2-719d-8e69-f13b35085564" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeStockOwnershipPlanESOPDisclosuresLineItems_019e6b08-eaf2-74c9-8a5e-51bdfaa35afe" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_019e6b08-eaf2-719d-8e69-f13b35085564" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_019edae0-467b-72b6-84b6-f5a4ecc3f0b2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeStockOwnershipPlanESOPDisclosuresLineItems_019e6b08-eaf2-74c9-8a5e-51bdfaa35afe" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_019edae0-467b-72b6-84b6-f5a4ecc3f0b2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_019e6b08-eaf2-7bcd-bc6d-8a977c7ec16c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeStockOwnershipPlanESOPDisclosuresLineItems_019e6b08-eaf2-74c9-8a5e-51bdfaa35afe" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_019e6b08-eaf2-7bcd-bc6d-8a977c7ec16c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ShareBasedCompensationArrangementByShareBasedPaymentAwardStockPlanOfferingPeriod_019e6b08-eaf2-7d7e-82c2-e5d242ad323d" xlink:href="dcth-20260630.xsd#dcth_ShareBasedCompensationArrangementByShareBasedPaymentAwardStockPlanOfferingPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeStockOwnershipPlanESOPDisclosuresLineItems_019e6b08-eaf2-74c9-8a5e-51bdfaa35afe" xlink:to="loc_dcth_ShareBasedCompensationArrangementByShareBasedPaymentAwardStockPlanOfferingPeriod_019e6b08-eaf2-7d7e-82c2-e5d242ad323d" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/NetLossIncomeperShareScheduleofPotentiallyDilutiveSecuritiesExcludedfromtheComputationofEarningsPerShareDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#NetLossIncomeperShareScheduleofPotentiallyDilutiveSecuritiesExcludedfromtheComputationofEarningsPerShareDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/NetLossIncomeperShareScheduleofPotentiallyDilutiveSecuritiesExcludedfromtheComputationofEarningsPerShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019e6b08-eaf2-74a8-9244-e1de40a3b4e8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019e6b08-eaf2-730e-92cd-230188e66a3e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019e6b08-eaf2-74a8-9244-e1de40a3b4e8" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019e6b08-eaf2-730e-92cd-230188e66a3e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019e6b08-eaf2-7013-bd30-38abd0fcc713" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019e6b08-eaf2-730e-92cd-230188e66a3e" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019e6b08-eaf2-7013-bd30-38abd0fcc713" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e6b08-eaf2-7013-bd30-38abd0fcc713_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019e6b08-eaf2-7013-bd30-38abd0fcc713" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e6b08-eaf2-7013-bd30-38abd0fcc713_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e6b08-eaf2-7559-a7e5-b979bb8c70d9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019e6b08-eaf2-7013-bd30-38abd0fcc713" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e6b08-eaf2-7559-a7e5-b979bb8c70d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockCompensationPlanMember_019e6b08-eaf2-77b6-8400-d926ed9a57d3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockCompensationPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e6b08-eaf2-7559-a7e5-b979bb8c70d9" xlink:to="loc_us-gaap_StockCompensationPlanMember_019e6b08-eaf2-77b6-8400-d926ed9a57d3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_019e6b08-eaf2-7996-b22a-d4e25cde68dd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e6b08-eaf2-7559-a7e5-b979bb8c70d9" xlink:to="loc_us-gaap_EmployeeStockMember_019e6b08-eaf2-7996-b22a-d4e25cde68dd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_019e6b08-eaf2-7a59-8ea5-bf841793c587" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019e6b08-eaf2-74a8-9244-e1de40a3b4e8" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_019e6b08-eaf2-7a59-8ea5-bf841793c587" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/CommitmentsandContingenciesDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#CommitmentsandContingenciesDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/CommitmentsandContingenciesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LossContingenciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingenciesTable_019e6b08-eaf2-7a6e-bc3d-10d1d9d99a17" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LossContingenciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:to="loc_us-gaap_LossContingenciesTable_019e6b08-eaf2-7a6e-bc3d-10d1d9d99a17" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_019e6b08-eaf2-792d-a677-22627fc0f37f" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LossContingenciesTable_019e6b08-eaf2-7a6e-bc3d-10d1d9d99a17" xlink:to="loc_srt_CounterpartyNameAxis_019e6b08-eaf2-792d-a677-22627fc0f37f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019e6b08-eaf2-792d-a677-22627fc0f37f_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_019e6b08-eaf2-792d-a677-22627fc0f37f" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019e6b08-eaf2-792d-a677-22627fc0f37f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019e6b08-eaf2-74ca-b7e7-cc95cf3ed9b5" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_019e6b08-eaf2-792d-a677-22627fc0f37f" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019e6b08-eaf2-74ca-b7e7-cc95cf3ed9b5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_MedacMember_019e6b08-eaf2-715d-97ed-467dac83ad98" xlink:href="dcth-20260630.xsd#dcth_MedacMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019e6b08-eaf2-74ca-b7e7-cc95cf3ed9b5" xlink:to="loc_dcth_MedacMember_019e6b08-eaf2-715d-97ed-467dac83ad98" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsAxis_019e6b08-eaf2-74cf-aee3-6055ad91394a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LossContingenciesTable_019e6b08-eaf2-7a6e-bc3d-10d1d9d99a17" xlink:to="loc_us-gaap_OtherCommitmentsAxis_019e6b08-eaf2-74cf-aee3-6055ad91394a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_019e6b08-eaf2-74cf-aee3-6055ad91394a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_OtherCommitmentsAxis_019e6b08-eaf2-74cf-aee3-6055ad91394a" xlink:to="loc_us-gaap_OtherCommitmentsDomain_019e6b08-eaf2-74cf-aee3-6055ad91394a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_019e6b08-eaf2-7291-b7d3-363bfe904790" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_OtherCommitmentsAxis_019e6b08-eaf2-74cf-aee3-6055ad91394a" xlink:to="loc_us-gaap_OtherCommitmentsDomain_019e6b08-eaf2-7291-b7d3-363bfe904790" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_AgreementsRelatingToClinicalTrialSupportMember_019e6b08-eaf2-77f5-9d3a-6c177463d270" xlink:href="dcth-20260630.xsd#dcth_AgreementsRelatingToClinicalTrialSupportMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsDomain_019e6b08-eaf2-7291-b7d3-363bfe904790" xlink:to="loc_dcth_AgreementsRelatingToClinicalTrialSupportMember_019e6b08-eaf2-77f5-9d3a-6c177463d270" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNet_019e6b08-eaf2-70f9-a64d-4d9893cf8f52" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccountsReceivableNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:to="loc_us-gaap_AccountsReceivableNet_019e6b08-eaf2-70f9-a64d-4d9893cf8f52" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_MilestonePaymentUnpaid_019e6b08-eaf2-7303-b6d8-e91d991e2c72" xlink:href="dcth-20260630.xsd#dcth_MilestonePaymentUnpaid"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:to="loc_dcth_MilestonePaymentUnpaid_019e6b08-eaf2-7303-b6d8-e91d991e2c72" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_TermOverWhichTheRoyaltyIsToBePaid_019e6b08-eaf2-7e4a-ba6e-438bb63e93be" xlink:href="dcth-20260630.xsd#dcth_TermOverWhichTheRoyaltyIsToBePaid"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:to="loc_dcth_TermOverWhichTheRoyaltyIsToBePaid_019e6b08-eaf2-7e4a-ba6e-438bb63e93be" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_MinimumAnnualPayments_019e6b08-eaf2-7bba-97d6-08f6b89ebc8e" xlink:href="dcth-20260630.xsd#dcth_MinimumAnnualPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:to="loc_dcth_MinimumAnnualPayments_019e6b08-eaf2-7bba-97d6-08f6b89ebc8e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingencyAccrualAtCarryingValue_019e6b08-eaf2-7ec4-8961-c5afb8135038" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LossContingencyAccrualAtCarryingValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:to="loc_us-gaap_LossContingencyAccrualAtCarryingValue_019e6b08-eaf2-7ec4-8961-c5afb8135038" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingencyAccrualCarryingValueNoncurrent_019e6b08-eaf2-7b05-8ae7-9af14ad78c38" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LossContingencyAccrualCarryingValueNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:to="loc_us-gaap_LossContingencyAccrualCarryingValueNoncurrent_019e6b08-eaf2-7b05-8ae7-9af14ad78c38" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingencyAccrualCarryingValueCurrent_019e6b08-eaf2-718d-bef7-9c7731a66b82" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LossContingencyAccrualCarryingValueCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:to="loc_us-gaap_LossContingencyAccrualCarryingValueCurrent_019e6b08-eaf2-718d-bef7-9c7731a66b82" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_SupplyAgreementRenewalOptionTerm_019e6b08-eaf2-7570-8ee3-f4429a2e81e9" xlink:href="dcth-20260630.xsd#dcth_SupplyAgreementRenewalOptionTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:to="loc_dcth_SupplyAgreementRenewalOptionTerm_019e6b08-eaf2-7570-8ee3-f4429a2e81e9" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PurchaseObligationDueInNextTwelveMonths_019e6b08-eaf2-7e25-a334-eac7b44e5ae5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PurchaseObligationDueInNextTwelveMonths"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:to="loc_us-gaap_PurchaseObligationDueInNextTwelveMonths_019e6b08-eaf2-7e25-a334-eac7b44e5ae5" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepositAssets_019e6b08-eaf2-7614-bbcc-35063be1048f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DepositAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_019e6b08-eaf2-767d-b63c-a06e97ba4bb7" xlink:to="loc_us-gaap_DepositAssets_019e6b08-eaf2-7614-bbcc-35063be1048f" xlink:type="arc" order="9"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/FairValueMeasurementsScheduleofLevel3InvestmentsDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#FairValueMeasurementsScheduleofLevel3InvestmentsDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/FairValueMeasurementsScheduleofLevel3InvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueDisclosureAssetAndLiabilityNotMeasuredAtFairValueLineItems_019e6b08-eaf2-7928-b8ba-aa9341570e78" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueDisclosureAssetAndLiabilityNotMeasuredAtFairValueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueDisclosureOfAssetAndLiabilityNotMeasuredAtFairValueTable_019e6b08-eaf2-7758-9dc5-97d3d0b06bc7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueDisclosureOfAssetAndLiabilityNotMeasuredAtFairValueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueDisclosureAssetAndLiabilityNotMeasuredAtFairValueLineItems_019e6b08-eaf2-7928-b8ba-aa9341570e78" xlink:to="loc_us-gaap_FairValueDisclosureOfAssetAndLiabilityNotMeasuredAtFairValueTable_019e6b08-eaf2-7758-9dc5-97d3d0b06bc7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByLiabilityClassAxis_019e6b08-eaf2-7682-97b2-3507dc959a6a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByLiabilityClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueDisclosureOfAssetAndLiabilityNotMeasuredAtFairValueTable_019e6b08-eaf2-7758-9dc5-97d3d0b06bc7" xlink:to="loc_us-gaap_FairValueByLiabilityClassAxis_019e6b08-eaf2-7682-97b2-3507dc959a6a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_019e6b08-eaf2-7682-97b2-3507dc959a6a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByLiabilityClassAxis_019e6b08-eaf2-7682-97b2-3507dc959a6a" xlink:to="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_019e6b08-eaf2-7682-97b2-3507dc959a6a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_019e6b08-eaf2-7321-a7b5-7d7733ac6cfe" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByLiabilityClassAxis_019e6b08-eaf2-7682-97b2-3507dc959a6a" xlink:to="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_019e6b08-eaf2-7321-a7b5-7d7733ac6cfe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_ContingentLiabilitiesMember_019e6b08-eaf2-7423-b05e-f0fc21311253" xlink:href="dcth-20260630.xsd#dcth_ContingentLiabilitiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_019e6b08-eaf2-7321-a7b5-7d7733ac6cfe" xlink:to="loc_dcth_ContingentLiabilitiesMember_019e6b08-eaf2-7423-b05e-f0fc21311253" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward_019e6b08-eaf2-73f0-9b9d-6d88d87573c8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueDisclosureAssetAndLiabilityNotMeasuredAtFairValueLineItems_019e6b08-eaf2-7928-b8ba-aa9341570e78" xlink:to="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward_019e6b08-eaf2-73f0-9b9d-6d88d87573c8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue_019e6b08-eaf2-70f5-9b8c-63b531ce12a3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward_019e6b08-eaf2-73f0-9b9d-6d88d87573c8" xlink:to="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue_019e6b08-eaf2-70f5-9b8c-63b531ce12a3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilitySettlements_019e6b08-eaf2-7fdd-a47d-b50250561222" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilitySettlements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward_019e6b08-eaf2-73f0-9b9d-6d88d87573c8" xlink:to="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilitySettlements_019e6b08-eaf2-7fdd-a47d-b50250561222" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityFairValueAdjustmentGainLossIncludedInEarnings_019e6b08-eaf2-7fff-8b0c-ee49ac8a94b1" xlink:href="dcth-20260630.xsd#dcth_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityFairValueAdjustmentGainLossIncludedInEarnings"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward_019e6b08-eaf2-73f0-9b9d-6d88d87573c8" xlink:to="loc_dcth_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityFairValueAdjustmentGainLossIncludedInEarnings_019e6b08-eaf2-7fff-8b0c-ee49ac8a94b1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityForeignExchangeGainLossIncludedInEarnings_019e6b08-eaf2-7326-97e4-a9ea87e02423" xlink:href="dcth-20260630.xsd#dcth_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityForeignExchangeGainLossIncludedInEarnings"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward_019e6b08-eaf2-73f0-9b9d-6d88d87573c8" xlink:to="loc_dcth_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityForeignExchangeGainLossIncludedInEarnings_019e6b08-eaf2-7326-97e4-a9ea87e02423" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue_019e6b08-eaf2-7c86-b123-1184b7778661" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/FairValueMeasurementsNarrativeDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#FairValueMeasurementsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/FairValueMeasurementsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019e6b08-eaf2-7b35-a728-423d8fffa8d5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019e6b08-eaf2-7e1c-8def-b589bb3b88be" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019e6b08-eaf2-7b35-a728-423d8fffa8d5" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019e6b08-eaf2-7e1c-8def-b589bb3b88be" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationByTypeAxis_019e6b08-eaf2-7864-94f4-586ff1b96b3e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContingentConsiderationByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019e6b08-eaf2-7e1c-8def-b589bb3b88be" xlink:to="loc_us-gaap_ContingentConsiderationByTypeAxis_019e6b08-eaf2-7864-94f4-586ff1b96b3e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationTypeDomain_019e6b08-eaf2-7864-94f4-586ff1b96b3e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContingentConsiderationTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ContingentConsiderationByTypeAxis_019e6b08-eaf2-7864-94f4-586ff1b96b3e" xlink:to="loc_us-gaap_ContingentConsiderationTypeDomain_019e6b08-eaf2-7864-94f4-586ff1b96b3e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationTypeDomain_019e6b08-eaf2-7176-bd55-ea98fc496d7b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContingentConsiderationTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ContingentConsiderationByTypeAxis_019e6b08-eaf2-7864-94f4-586ff1b96b3e" xlink:to="loc_us-gaap_ContingentConsiderationTypeDomain_019e6b08-eaf2-7176-bd55-ea98fc496d7b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_UnobservableInputsInValuationMember_019e6b08-eaf2-7904-9b7f-41f55a46c102" xlink:href="dcth-20260630.xsd#dcth_UnobservableInputsInValuationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ContingentConsiderationTypeDomain_019e6b08-eaf2-7176-bd55-ea98fc496d7b" xlink:to="loc_dcth_UnobservableInputsInValuationMember_019e6b08-eaf2-7904-9b7f-41f55a46c102" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeAxis_019e6b08-eaf2-7b24-9bcb-965a0484e490" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019e6b08-eaf2-7e1c-8def-b589bb3b88be" xlink:to="loc_us-gaap_MeasurementInputTypeAxis_019e6b08-eaf2-7b24-9bcb-965a0484e490" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_019e6b08-eaf2-7b24-9bcb-965a0484e490_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_019e6b08-eaf2-7b24-9bcb-965a0484e490" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_019e6b08-eaf2-7b24-9bcb-965a0484e490_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_019e6b08-eaf2-729a-816d-28f61a77d216" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_019e6b08-eaf2-7b24-9bcb-965a0484e490" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_019e6b08-eaf2-729a-816d-28f61a77d216" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_MeasurementInputProbabilityOfPaymentMember_019e6b08-eaf2-70e3-beb0-99b924bcfc7e" xlink:href="dcth-20260630.xsd#dcth_MeasurementInputProbabilityOfPaymentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_019e6b08-eaf2-729a-816d-28f61a77d216" xlink:to="loc_dcth_MeasurementInputProbabilityOfPaymentMember_019e6b08-eaf2-70e3-beb0-99b924bcfc7e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputDiscountRateMember_019e6b08-eaf2-7f26-a6e8-90ba104ea691" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputDiscountRateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_019e6b08-eaf2-729a-816d-28f61a77d216" xlink:to="loc_us-gaap_MeasurementInputDiscountRateMember_019e6b08-eaf2-7f26-a6e8-90ba104ea691" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputExpectedTermMember_019e6b08-eaf2-719b-b697-304d1cdce8d7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputExpectedTermMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_019e6b08-eaf2-729a-816d-28f61a77d216" xlink:to="loc_us-gaap_MeasurementInputExpectedTermMember_019e6b08-eaf2-719b-b697-304d1cdce8d7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationTechniqueAxis_019e6b08-eaf2-77d9-91ae-cd68a3fb7b44" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationTechniqueAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019e6b08-eaf2-7e1c-8def-b589bb3b88be" xlink:to="loc_us-gaap_ValuationTechniqueAxis_019e6b08-eaf2-77d9-91ae-cd68a3fb7b44" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationTechniqueDomain_019e6b08-eaf2-77d9-91ae-cd68a3fb7b44_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationTechniqueDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ValuationTechniqueAxis_019e6b08-eaf2-77d9-91ae-cd68a3fb7b44" xlink:to="loc_us-gaap_ValuationTechniqueDomain_019e6b08-eaf2-77d9-91ae-cd68a3fb7b44_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationTechniqueDomain_019e6b08-eaf2-70cd-b01d-3d9f7263539f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationTechniqueDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ValuationTechniqueAxis_019e6b08-eaf2-77d9-91ae-cd68a3fb7b44" xlink:to="loc_us-gaap_ValuationTechniqueDomain_019e6b08-eaf2-70cd-b01d-3d9f7263539f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationTechniqueDiscountedCashFlowMember_019e6b08-eaf2-78b1-9d11-43b29493b63e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationTechniqueDiscountedCashFlowMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationTechniqueDomain_019e6b08-eaf2-70cd-b01d-3d9f7263539f" xlink:to="loc_us-gaap_ValuationTechniqueDiscountedCashFlowMember_019e6b08-eaf2-78b1-9d11-43b29493b63e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_019e6b08-eaf2-7f83-b227-6b63d8384c46" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019e6b08-eaf2-7e1c-8def-b589bb3b88be" xlink:to="loc_srt_RangeAxis_019e6b08-eaf2-7f83-b227-6b63d8384c46" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019e6b08-eaf2-7f83-b227-6b63d8384c46_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_019e6b08-eaf2-7f83-b227-6b63d8384c46" xlink:to="loc_srt_RangeMember_019e6b08-eaf2-7f83-b227-6b63d8384c46_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019e6b08-eaf2-7bc6-a297-4bf3678b45db" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_019e6b08-eaf2-7f83-b227-6b63d8384c46" xlink:to="loc_srt_RangeMember_019e6b08-eaf2-7bc6-a297-4bf3678b45db" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_019e6b08-eaf2-7db4-872f-ea10644d60fe" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019e6b08-eaf2-7bc6-a297-4bf3678b45db" xlink:to="loc_srt_MinimumMember_019e6b08-eaf2-7db4-872f-ea10644d60fe" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_019e6b08-eaf2-79e7-a30b-d0749c6d24d9" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019e6b08-eaf2-7bc6-a297-4bf3678b45db" xlink:to="loc_srt_MaximumMember_019e6b08-eaf2-79e7-a30b-d0749c6d24d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityMeasurementInput_019e6b08-eaf2-7a4d-932f-994de88e3ec6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityMeasurementInput"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019e6b08-eaf2-7b35-a728-423d8fffa8d5" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityMeasurementInput_019e6b08-eaf2-7a4d-932f-994de88e3ec6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dcth_BusinessCombinationContingentConsiderationLiabilityMeasurementPeriod_019e6b08-eaf2-7893-a23f-c0821ac08600" xlink:href="dcth-20260630.xsd#dcth_BusinessCombinationContingentConsiderationLiabilityMeasurementPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019e6b08-eaf2-7b35-a728-423d8fffa8d5" xlink:to="loc_dcth_BusinessCombinationContingentConsiderationLiabilityMeasurementPeriod_019e6b08-eaf2-7893-a23f-c0821ac08600" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/FairValueMeasurementsScheduleofFinancialAssetsandLiabilitiesMeasuredatFairValueDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#FairValueMeasurementsScheduleofFinancialAssetsandLiabilitiesMeasuredatFairValueDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/FairValueMeasurementsScheduleofFinancialAssetsandLiabilitiesMeasuredatFairValueDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019e6b08-eaf2-7836-b02b-6ec458868f60" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019e6b08-eaf2-758a-8c88-4063a47ce8bc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019e6b08-eaf2-7836-b02b-6ec458868f60" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019e6b08-eaf2-758a-8c88-4063a47ce8bc" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e6b08-eaf2-7d0d-bb2d-0e7d6c6d511b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_019e6b08-eaf2-758a-8c88-4063a47ce8bc" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e6b08-eaf2-7d0d-bb2d-0e7d6c6d511b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e6b08-eaf2-7d0d-bb2d-0e7d6c6d511b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e6b08-eaf2-7d0d-bb2d-0e7d6c6d511b" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e6b08-eaf2-7d0d-bb2d-0e7d6c6d511b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e6b08-eaf2-7ffe-b3cb-4268432bef9a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e6b08-eaf2-7d0d-bb2d-0e7d6c6d511b" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e6b08-eaf2-7ffe-b3cb-4268432bef9a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_019e6b08-eaf2-7bd7-9e78-49d657a155a3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e6b08-eaf2-7ffe-b3cb-4268432bef9a" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_019e6b08-eaf2-7bd7-9e78-49d657a155a3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_019e6b08-eaf2-79d5-9e64-88fc0cf1b2b1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e6b08-eaf2-7ffe-b3cb-4268432bef9a" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_019e6b08-eaf2-79d5-9e64-88fc0cf1b2b1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_019e6b08-eaf2-71fc-aeb4-fc471f68eed1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e6b08-eaf2-7ffe-b3cb-4268432bef9a" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_019e6b08-eaf2-71fc-aeb4-fc471f68eed1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosureAbstract_019e6b08-eaf2-7b35-ab2a-d1df46026643" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019e6b08-eaf2-7836-b02b-6ec458868f60" xlink:to="loc_us-gaap_AssetsFairValueDisclosureAbstract_019e6b08-eaf2-7b35-ab2a-d1df46026643" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_019e6b08-eaf2-7674-b3d1-203ccb46accc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_019e6b08-eaf2-7b35-ab2a-d1df46026643" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_019e6b08-eaf2-7674-b3d1-203ccb46accc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019e6b08-eaf2-7c30-a45a-cc55ca7ffeac" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_019e6b08-eaf2-7b35-ab2a-d1df46026643" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019e6b08-eaf2-7c30-a45a-cc55ca7ffeac" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_019e6b08-eaf2-7390-a2c1-6a303c513266" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_019e6b08-eaf2-7b35-ab2a-d1df46026643" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_019e6b08-eaf2-7390-a2c1-6a303c513266" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_019e6b08-eaf2-7733-90d8-380e5406f6b8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_019e6b08-eaf2-7836-b02b-6ec458868f60" xlink:to="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_019e6b08-eaf2-7733-90d8-380e5406f6b8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_019e6b08-eaf2-7091-8fa8-486b59f8755c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_019e6b08-eaf2-7733-90d8-380e5406f6b8" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_019e6b08-eaf2-7091-8fa8-486b59f8755c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosure_019e6b08-eaf2-7902-870d-14a039bdc8b3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_019e6b08-eaf2-7733-90d8-380e5406f6b8" xlink:to="loc_us-gaap_LiabilitiesFairValueDisclosure_019e6b08-eaf2-7902-870d-14a039bdc8b3" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.delcath.com/role/SegmentInformationScheduleofRevenuebyLocationDetails" xlink:type="simple" xlink:href="dcth-20260630.xsd#SegmentInformationScheduleofRevenuebyLocationDetails"/>
  <link:definitionLink xlink:role="http://www.delcath.com/role/SegmentInformationScheduleofRevenuebyLocationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationLineItems_019e6b08-eaf2-7ce3-bd54-db3d63a98804" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentReportingInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019e6b08-eaf2-7499-9ba3-aa01e8f505f2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019e6b08-eaf2-7ce3-bd54-db3d63a98804" xlink:to="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019e6b08-eaf2-7499-9ba3-aa01e8f505f2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_019e6b08-eaf2-7cfc-81b9-1909154c2d89" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019e6b08-eaf2-7499-9ba3-aa01e8f505f2" xlink:to="loc_srt_StatementGeographicalAxis_019e6b08-eaf2-7cfc-81b9-1909154c2d89" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019e6b08-eaf2-7cfc-81b9-1909154c2d89_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_019e6b08-eaf2-7cfc-81b9-1909154c2d89" xlink:to="loc_srt_SegmentGeographicalDomain_019e6b08-eaf2-7cfc-81b9-1909154c2d89_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019e6b08-eaf2-7f91-ba8b-9083cee35fa9" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_019e6b08-eaf2-7cfc-81b9-1909154c2d89" xlink:to="loc_srt_SegmentGeographicalDomain_019e6b08-eaf2-7f91-ba8b-9083cee35fa9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonUsMember_019e6b08-eaf2-7376-810d-e25042608bba" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NonUsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019e6b08-eaf2-7f91-ba8b-9083cee35fa9" xlink:to="loc_us-gaap_NonUsMember_019e6b08-eaf2-7376-810d-e25042608bba" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_country_US_019e6b08-eaf2-77d1-aa11-11f1582c6865" xlink:href="https://xbrl.sec.gov/country/2026/country-2026.xsd#country_US"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019e6b08-eaf2-7f91-ba8b-9083cee35fa9" xlink:to="loc_country_US_019e6b08-eaf2-77d1-aa11-11f1582c6865" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019e6b08-eaf2-7cba-b974-e9e6f3e15dc5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019e6b08-eaf2-7ce3-bd54-db3d63a98804" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019e6b08-eaf2-7cba-b974-e9e6f3e15dc5" xlink:type="arc" order="0"/>
  </link:definitionLink>
</link:linkbase>
