Lanthanide-doped　inorganic　nanocrystals　have　attracted　extensive　attention　due　to　their　long　luminescence　lifetime　and　large　Stokes　shift.　In　this　work,　an　immunosensing　platform　based　on　CePO4:Tb　(CPOT)　was　successfully　constructed,　which　could　avoid　the　autofluorescence　interference　of　complex　biological　matrices.　Specifically,　CPOT　was　synthesized　by　a　solvothermal　method,　which　exhibited　H2O2-responsive　luminescence　behavior.　Taking　advantage　of　this　feature,　an　autofluorescence-free　immunosensor　with　CPOT　as　the　probe　and　H2O2　as　the　quencher　was　developed　to　detect　prostate-specific　antigen　(PSA).　Functionalized　liposomes　were　used　to　encapsulate　glucose　oxidase　(GOD)　and　labeled　on　detection　antibodies　to　improve　the　sensitivity　of　the　probe.　Under　the　proven　optimal　experimental　conditions,　the　developed　autofluorescence-free　immunosensor　exhibited　a　linear　luminescence　response　to　the　logarithm　of　PSA　concentration　(0.005-25　ng　mL−1)　with　a　limit　of　detection　(LOD)　of　3.25　pg　mL−1.　The　performance　shows　that　the　autofluorescence-free　immunosensor　based　on　this　strategy　opens　up　a　new　field　of　vision　for　clinical　PSA　detection.　©　2022　The　Royal　Society　of　Chemistry.