A　new　signal-on　immunoassay　protocol　for　sensitive　electronic　detection　of　alpha-fetoprotein　(AFP)　was　developed　by　1　coupling　with　metal　sulfide　nanolabels　and　a　silver　nanocluster　(AgNC)-based　rolling　circle　amplification　(RCA)　strategy.　Initially,　a　sandwiched　immunocomplex　was　formed　on　a　primary　antibody-coated　microplate　using　a　PbS　nanoparticle-labeled　polyclonal　anti-AFP　antibody　(PbS-pAb(2))　as　the　detection　antibody,　and　then　the　carried　PbS-pAb(2)　was　dissolved　by　acid　to　release　a　large　number　of　lead　ions,　which　could　induce　the　cleavage　of　lead-specific　DNAzyme　immobilized　on　the　electrode.　The　residual　single-stranded　DNA　on　the　electrode　could　be　used　as　the　primer　to　produce　numerous　repeated　oligonucleotide　sequences　via　the　RCA　reaction　for　the　hybridization　with　many　AgNC-labeled　detection　probes,　resulting　in　the　amplification　of　the　electronic　signal　due　to　the　unique　properties　of　silver　nanoclusters.　Under　optimal　conditions,　the　developed　immunoassay　exhibited　high　sensitivity　for　the　detection　of　AFP　with　a　dynamic　range　of　0.001-200　ng　mL(-1)　and　a　detection　limit　(LOD)　of　0.8　pg　mL(-1).　Intra-assay　and　interassay　coefficients　of　variation　were　below　8.0%　and　10%,　respectively.　Importantly,　the　methodology　was　evaluated　by　analyzing　12　clinical　serum　specimens,　and　no　significant　differences　were　encountered　in　comparison　with　the　conventional　enzyme-linked　immunosorbent　assay　(ELISA)　method.