Abstract: In this work, polydopamine nano-microspheres with good biocompatibility were prepared by the biomimetic dopamine self-polymerization. Silver nanoparticles were modified on the polydopamine microspheres. The composite microspheres show good catalytic performance towards the reduction of H₂O₂ and binding capacity with biomolecules. An electrochemical immunosensor was proposed using amino functional graphene as the substrate material and composite microspheres as labels. Cyclic voltammetry and chronoamperometry were used to investigate the performance of electrochemical immunosensor. Under optimal conditions, the linear range of the immunosensor was 0.1 pg/mL~15 ng/mL with a detection limit of 0.025 pg/mL.