A novel and simple electrochemical immunoassay for C-reactive protein was developed using metal-organic frameworks (Au-MOFs) as signal unit. In this study, we found MOFs could be used as signal probe. And this new class of signal probe differs from traditional probe. The signal of the copper ions (Cu2+) from MOFs could be directly detected without acid dissolution and preconcentration, which would greatly simplify the detection steps and reduce the detection time. Moreover, MOFs contain large amounts of Cu2+ ions, providing high electrochemical signals. Our report represents the first example of using MOFs themselves as electrochemical signal probe for biosensors. Platinum nanoparticle modified covalent organic frameworks (Pt-COFs) with high electronic conductivity was employed as the substrate, which is the first time demonstrating the use of Pt-COFs for electrochemical immunoassay. Under the optimized experimental conditions, the proposed sensing strategy provides a linear dynamic ranging from 1 to 400 ng/mL. A detection limit of 0.2 ng/mL was obtained, indicating an improved analytical performance. With these merits, this stable, simple, low-cost, sensitive and selective electrochemical immunoassay shows promise for applications in the point-of-care diagnostics of dieses and environmental monitoring.