This　work　developed　a　near-infrared　(near-IR)　light-activated　non-enzymatic　signal-off　photoelectrochemical　(PEC)　immunoassay　for　the　ultrasensitive　detection　of　α-fetoprotein　(AFP)　on　the　basis　of　branched　polyethylenimine　(BPEI)-modified　upconversion　nanoparticle　(UCNP)@CdTe　quantum　dot　(QD)　nanostructures　by　coupling　with　the　synergistic　effect　of　dual-purpose　copper　ions.　Emission　light　originated　from　NaYF　4　:Yb,Er　UCNP　was　directly　utilized　through　the　electrostatic　bonding　of　CdTe　QDs　to　excite　the　separation　of　electron-hole　pairs,　resulting　in　the　generation　of　obvious　photocurrent　under　a　980　nm　laser.　By　using　polyclonal　antibody-labeled　cupric　oxide　nanoparticle　as　the　secondary　antibody,　the　nanolabel　was　introduced　into　the　monoclonal　anti-AFP　antibody-modified　microplates　in　the　presence　of　target　AFP.　After　treatment　with　acid,　the　as-released　copper　ion　decreased　the　photocurrent　through　the　synergistic　effect　with　two　issues:　One　was　initially　to　form　coordination　with　BPEI　on　the　surface　of　UCNP,　and　then　the　near-IR　excitation　light　and　upconversion　luminescence　were　attenuated　due　to　the　internal　filter　effect;　another　was　to　snatch　the　electrons　flowing　from　the　valence　band　of　CdTe　QD　as　the　exciton　trapping　sites.　Under　optimal　conditions,　the　dual-purpose　Cu　2+　-activated　signal-off　PEC　immunosensing　platform　exhibited　a　dynamic　linear　range　from　10　pg　mL　-1　to　50　ng　mL　-1　,　accompanying　the　decreasing　photocurrent　with　the　increment　of　AFP　concentration　at　an　experimental　detection　limit　of　1.2　pg　mL　-1　.　Importantly,　good　accuracy　was　achieved　by　this　method　in　comparison　with　the　results　with　human　AFP　ELISA　kit　for　analysis　of　human　serum　samples.　This　dual-purpose　Cu　2+　-activated　PEC　immunoassay　brings　a　promising,　enzyme-free　and　innovative　thinking　for　the　detection　of　low-abundance　biomarkers.　©　2019　American　Chemical　Society.