This　work　reports　a　novel　electrochemical　immunoassay　protocol　with　signal　amplification　for　determination　of　proteins　(human　IgG　here　used　as　a　model　target　analyte)　at　an　ultralow　concentration　using　DNA-based　hybridization　chain　reaction　(HCR).　The　immuno-HCR　assay　consists　of　magnetic　immunosensing　probes,　nanogold-labeled　signal　probes　conjugated　with　the　DNA　initiator　strands,　and　two　different　hairpin　DNA　molecules.　The　signal　is　amplified　by　the　labeled　ferrocene　on　the　hairpin　probes.　In　the　presence　of　target　IgG,　the　sandwiched　immunocomplex　can　be　formed　between　the　immobilized　antibodies　on　the　magnetic　beads　and　the　signal　antibodies　on　the　gold　nanoparticles.　The　carried　DNA　initiator　strands　open　the　hairpin　DNA　structures　in　sequence　and　propagate　a　chain　reaction　of　hybridization　events　between　two　alternating　hairpins　to　form　a　nicked　double-helix.　Numerous　ferrocene　molecules　are　formed　on　the　neighboring　probe,　each　of　which　produces　an　electrochemical　signal　within　the　applied　potentials.　Under　optimal　conditions,　the　immuno-HCR　assay　presents　good　electrochemical　responses　for　determination　of　target　IgG　at　a　concentration　as　low　as　0.1　fg　mL(-1).　Importantly,　the　methodology　can　be　further　extended　to　the　detection　of　other　proteins　or　biomarkers.