The　development　of　rapid　and　sensitive　CA19–9　(carbohydrate　antigen　19–9)　analytical　methods　for　early　screening　of　potential　patients,　especially　in　clinical　situations,　is　important　for　controlling　the　progression　of　pancreatic　cancer.　Herein,　a　new　photoelectrochemical　(PEC)　immunoassay　has　been　devised　for　the　ultrasensitive　detection　of　CA19–9　using　gold　nanoparticle-modified　ultrathin　ZnIn2S4　nanosheets　(Au-UZNS)　as　the　photoactive　substrate.　Notably,　the　alkaline　phosphatase　(ALP)　labeled　on　the　detection　antibody　(ALP-dAb)　serves　as　the　signal　amplifier　that　catalyzes　the　production　of　large　amounts　of　ascorbic　acid　(AA)　after　the　sandwiched　immunoreaction.　The　generated　AA　is　an　outstanding　electron　donor,　thereby　improving　the　intensity　of　the　photoactive　substrate.　Under　the　optimized　parameters,　the　Au-UZNS-based　PEC　immunosensor　displays　an　excellent　response　to　CA19–9　ranging　from　0.01　to　500　U　mL　−1　with　a　limit　of　detection　(LOD)　of　4.7　mU　mL　−1.　Generally,　the　CA19–9　levels　in　the　serum　of　high-risk　pancreatic　cancer　patients　range　from　120　to　400　U　mL−1,　while　the　levels　in　normal　humans　range　from　0　to　40　U　mL−1.　Therefore,　the　exceptionally　low　LOD　value　of　the　proposed　method　is　sufficient　to　meet　the　threshold　for　clinical　detection　and　holds　significant　potential　for　further　application.　©　2025　Elsevier　B.V.