A photocurrent　enhancing　photoelectrochemical　(PEC)　immunosensor　was　developed for　chloramphenicol　(CAP)　detection　based　on　cation　exchange　reaction.　The　efficient　split-type　PEC　immunosensor　combined　with　controlled-release　strategy　was　established　using　the　ZnIn2S4/TiO2/Ti3C2　MXene　(ZIS/T/M)　composite　as　the　photoactive　material　and　CuO　as　the　signal　response　probe.　In　the　presence　of　target　CAP,　CuO-labeled　CAP　antibody　(CuO-mAb)　was　introduced　onto　the　microplate　via　a　competitive-type　immunoassay.　Under　acidic　conditions,　a　large　amount　of　Cu2+　released　from　CuO-mAb,　which　triggered　a　cation　exchange　reaction　with　the　Zn2+　in　ZIS/T/M-modified　photoelectrode　to　generate　CuxS,　resulting　in　enhancing the　photocurrent.　As　a　result,　the　quantitative　detection　of　CAP　was　achieved　by　detecting　the　photocurrent　change.　Under　optimized　conditions,　the　linear　range　of　the　sensor　was　1 pg/mL　to　50 ng/mL,　and　the　detection　limit　was　0.24 pg/mL.　The　excellent　PEC　behavior　of　ZIS/T/M　composite　could　be　attributed　to　the　fact　that　heterojunction　formation　improved　the　migration　and　separation　of　the photocarrier.　Additionally,　by　virtue　of　the　photocurrent-enhancing　strategy　via　cation　exchange　reaction　and　the　controlled　releasing　signal　amplification　method　of　ion,　the　PEC　immunosensor　has　high　sensitivity　and　satisfactory　accuracy,　offering　great　potential　applications　in　the　determination of　CAP.　Graphical　Abstract:　(Figure　presented.)　©　The　Author(s),　under　exclusive　licence　to　Springer-Verlag　GmbH　Austria,　part　of　Springer　Nature　2024.