A　nanoparticle-based　potentiometric　immunoassay　was　designed　for　the　sensitive　detection　of　squamous　cell　carcinoma　antigen　(SCCA;　cervical　carcinoma　marker)　on　a　portable　pH　meter　coupling　enzyme-labeled　hybridization　chain　reaction　(HCR)　with　two　alternating　hairpin　DNA　probes　for　the　signal　amplification.　Initially,　a　sandwich-type　immunoreaction　was　carried　out　between　anti-SCCA　capture　antibody-conjugated　magnetic　bead　and　detection　antibody/initiator　strand-coated　gold　nanoparticle　(AuNP).　Then.　the　HCR　reaction　was　readily　executed　between　two　glucose　oxidase　(GOx)-labeled　hairpins　through　the　initiator　strand　to　form　numerous　GOx　concatamers　on　the　AuNP　via　the　long　nicked　double-helix.　The　concatenated　GOx　oxidized　glucose　into　gluconic　acid　and　hydrogen　peroxide,　thus　resulting　in　the　pH　change　of　the　detection　solution　on　a　handheld　pH　meter.　Several　labeling　protocols　including　GOx-antibody,　GOx-AuNP-antibody　and　GOx-HCR-AuNP-antibody　were　investigated　for　detection　of　target　SCCA,　and　improved　analytical　features　were　obtained　with　the　immune-HCR　assay.　Under　optimum　conditions,　the　immune-HCR　assay　exhibited　good　pH　responses　for　the　determination　of　SCCA　at　a　concentration　as　low　as　5.7　pg/mL.　Additionally,　the　immune-HCR　assay　had　good　precision　and　reproducibility,　high　specificity,　and　acceptable　accuracy　for　analyzing　human　serum　specimens.　(C)　2019　Chinese　Chemical　Society　and　Institute　of　Materia　Medica,　Chinese　Academy　of　Medical　Sciences.　Published　by　Elsevier　B.V.　All　rights　reserved.