Cation　exchange　(CE)　is　a　burgeoning　method　for　controlled　crystal　synthesis;　however,　its　applications　in　bioanalysis　are　still　in　their　infancy.　Herein,　we　explored　the　transformation　of　ZnIn2S4　in　properties　after　the　CE　reaction　with　Cu2+　ions;　furthermore,　the　discrepancy　was　employed　to　design　a　dual-readout　detection　system　of　photothermal　and　polarity-switchable　photoelectrochemical　(PEC)　immunoassays　to　realize　reliable　detection　of　carcinoembryonic　antigen　(CEA).　In　the　presence　of　CEA,　the　CuO　nanoparticles　(CuO　NPs)　employed　as　dual-signal　response　probes　would　bond　to　the　microplates　and　be　acidolyzed　by　HCl　to　release　Cu2+,　which　could　replace　Zn2+　and　In3+　via　the　CE　reaction.　After　the　CE　reaction　is　completed,　the　photocurrent　would　switch　from　a　weak　anodic　photocurrent　to　a　cathode　one　by　using　a　635　nm　laser　as　a　signal　amplifier,　while　the　photothermal　signal　would　be　enhanced　with　808　nm　laser　illumination.　On　the　basis　of　the　polarity-switchable　PEC　strategy,　CEA　could　be　accurately　detected　from　0.1　to　50　ng　mL(-1)　with　a　limit　of　detection　(LOD)　of　48　pg　mL(-1)　(S/N　=　3).　Moreover,　the　photothermal　assay　for　CEA　detection　possesses　a　linear　range　from　0.5　to　100　ng　mL(-1)　with　a　LOD　of　0.21　ng　mL(-1).　In　addition,　the　designed　sensing　platform　only　relies　on　devices　with　portability　that　are　permitted　for　point-of-care　detection.