The　yolk-shell　structure　has　become　a　research　hotspot　in　the　field　of　photocatalysis　in　recent　years　due　to　its　stability,　movable　yolk,　and　internal　voids.　However,　yolk-shell　has　not　been　fully　explored　and　applied　in　photoelectrochemical　(PEC)　immunoassays.　In　this　work,　a　smartphone-based　portable　PEC　immunoassay　was　constructed　by　using　high-entropy　yolk-shell　Au@(ZnCdMnGaCu)xS　as　a　photosensitive　material,　showing　satisfactory　detection　with　the　assistance　of　localized　surface　plasmon　resonance　(LSPR).　Specifically,　a　typical　sandwich　reaction　introduces　a　detection　antibody　modified　and　labeled　with　gold　nanoparticles　(Au　NPs)　of　alkaline　phosphatase　(ALP)　into　the　system　with　the　presence　of　prostate-specific　antigen　(PSA).　Ascorbic　acid　(AA)　content　increased　with　increasing　PSA　and　showed　a　linear　enhancement　of　photocurrent　at　PSA　concentrations　of　0.01–50　ng　mL−1　with　a　limit　of　detection　of　8.94　pg　mL−1.　Additionally,　the　proposed　assay　technology　not　only　provides　a　portable　detection　system　for　the　immediate　detection　of　tumor　markers,　but　also　offers　a　promising　paradigm　for　the　development　of　high-entropy　materials.　©　2024　Elsevier　B.V.