Methods　based　on　nanostructures　have　been　developed　for　potentiometric　immunosensors,　but　most　involve　low　sensitivity　or　weak　signal　output　and　are　unsuitable　for　routine　use　in　diagnosis.　Herein,　we　devise　an　in-situ　signal-amplification　strategy　for　enhanced　electrical　readout　of　potentiometric　immunosensor　toward　target　prostate-specific　antigen　(PSA,　one　kind　of　cancer　biomarkers),　based　on　polyion　oligonucleotide-labeled　gold　nanoparticles　(AuNPs).　To　decrease　the　background　signal,　monoclonal　anti-human　PSA　capture　antibody　was　covalently　conjugated　onto　an　activated　glassy　carbon　electrode　via　typical　carbodiimide　coupling.　AuNPs　heavily　functionalized　with　the　polyion　oligonucleotides　and　polyclonal　anti-PSA　detection　antibodies　(pAb2-AuNP-DNA)　were　utilized　as　the　signal-generation　nanotags.　In　the　presence　of　target　PSA,　a　sandwich-type　immunoreaction　was　executed　between　capture　antibody　and　detection　antibody　on　the　electrode.　The　detectable　signal　derived　from　the　shift　in　the　electric　potential　as　a　result　of　the　change　in　the　surface　charge　before　and　after　the　antigen-antibody　reaction.　With　target　PSA　increased,　the　captured　pAb2-AuNP-DNA　to　the　electrode　accompanying　detection　antibody　increased,　thereby　resulting　in　the　change　of　the　electrode　potential.　Due　to　numerous　polyion　oligonucleotides　with　the　negative　charge,　the　signal　readout　amplified.　Under　the　optimal　conditions,　the　shift　in　the　output　potential　was　proportional　to　the　logarithm　of　target　PSA　concentration　and　displayed　a　dynamic　linear　range　from　0.05　to　20 ng mL−1　with　a　detection　limit　of　13.6 pg mL−1.　An　intermediate　precision　of　≤13.2%　was　accomplished　with　the　batch-to-batch　identification.　The　selectivity　was　acceptable.　The　method　accuracy　was　evaluated　for　human　serum　specimens,　and　gave　the　consistent　results　between　the　potentiometric　immunosensor　and　the　referenced　enzyme-linked　immunosorbent　assay　(ELISA).　©　2017　Elsevier　B.V.