Development　of　high-precision　human　epidermal　growth　factor　receptor　2　(HER2)　assay　is　essential　for　the　early　diagnostic　and　prevention　of　breast　cancer.　In　this　work,　an　innovative　Fe/Mn　bimetallic　nanozyme　at　the　edge　of　N-doped　carbon　defects　(FeMn-NCedge)　with　abundant　active　sites　was　prepared　through　the　hydrothermal　synthetic　method.　FeMn-NCedge　nanozyme　displayed　excellent　peroxidase-like　activity　relative　to　the　H2O2-catalyzed　3,3′,5,5′-tetramethylbenzidine　(TMB)　system　for　generation　of　the　oxidized　TMB　(oxTMB).　As　a　proof-of-concept　application,　we　constructed　an　electrochemical　immunoassay　for　the　detection　of　HER2　based　on　the　unique　merits　of　FeMn-NCedge.　Initially,　a　sandwiched　immunoreaction　was　carried　out　in　the　microtiter　plate　coated　with　monoclonal　anti-HER2　capture　antibodies　using　glucose　oxidase　(GOx)-labeled　anti-HER2　as　detection　antibody.　The　carried　GOx　could　catalyze　glucose　to　produce　H2O2,　thus　resulting　in　the　formation　of　oxTMB　with　the　assistance　of　TMB　and　FeMn-NCedge　nanozyme.　The　produced　oxTMB　could　be　determined　on　the　electrode　by　the　chronoamperometry　at　an　applied　potential　of　+10　mV.　Experimental　results　revealed　that　the　steady-state　current　increased　with　the　increasing　HER2　concentration　in　the　sample,　and　gave　a　good　linear　relationship　within　the　dynamic　range　of　0.01–10　ng/mL　at　a　limit　of　detection　of　5.4　pg/mL　HER2.　In　addition,　good　reproducibility,　high　specificity　and　acceptable　accuracy　were　acquired　for　the　measurement　of　human　serum　samples.　Importantly,　this　method　can　be　extended　for　quantitative　monitoring　other　disease-related　proteins　by　changing　the　corresponding　antibodies.　©　2023　Elsevier　B.V.