This　work　reports　on　an　ultrasensitive　photoelectrochemical　(PEC)　aptasensor　for　the　detection　of　8-hydroxy-2′-deoxyguanosine　(8-OHdG)　by　using　target-triggered　hemin/G-quadruplex　photocurrent　polarity　switching　on　ultrathin　ZnIn2S4　nanosheets　(ZISNS).　Hemin/G-quadruplexes　were　assembled　on　indium　tin　oxide　(ITO)　electrodes　coated　with　gold　nanoparticle-modified　ZISNS　(AuNPs-ZISNS)　as　signaling　labels　for　the　polarity　inversion　mechanism　in　PEC　aptasensors.　Benefiting　from　the　excellent　photoelectronic　properties　of　AuNPs-ZISNS　and　the　photocurrent　polarity　switching　reliability　of　hemin,　the　proposed　aptasensor　for　8-OHdG　detection　was　in　a　broad　range　from　1.0　pM　to　10,000　pM　with　a　detection　limit　of　0.3　pM.　Moreover,　this　assay　has　shown　sufficient　sensitivity,　favorable　stability,　and　high　selectivity　in　the　detection　of　complex　biological　matrices.　The　recoveries　were　in　the　range　of　92–108%,　and　the　relative　standard　derivations　(RSD)　were　ranged　from　2.1%　to　5.1%,　indicating　the　good　accuracy　and　high　precision　of　this　approach.　Impressively,　the　concept　of　photocurrent-polarity-switching　mode　provides　an　alternative　for　constructing　accurate　and　plausible　PEC　bioanalysis　and　inspires　more　interest　in　the　design　of　advanced　PEC　bioanalysis　through　readout　signal　regulation.　©　2022　Elsevier　B.V.