A novel electrochemical immunosensor with poly(vinyl pyrrolidone)-tungsten disulfide (PVP/WS 2 ) nanosheets electrode was fabricated for fibroblast growth factor 21 (FGF-21) detection based on gold nanoparticles and metal organic framework (AuNPs/MOFs) nanozyme. The PVP/WS 2 nanosheets enabled direct antibody immobilization on the electrode surface and exhibited high conductivity. The MOFs nanozyme peroxidase-like activity efficiently converted a o-phenylenediamine substrate to 2,2-diaminoazobenzene, which generated an ideal electrochemical signal for monitoring FGF-21 concentrations. The electrochemical immunosensor was fully characterized via Impedance spectroscopy (EIS), Cyclic voltammetry (CV), Squarewave voltammetry (SWV), Scanning electron microscope (SEM), Transmission electron microscope (TEM) and ultraviolet-visible spectroscopy (UV-vis). The biosensor exhibited a good linear relationship over the range 1 pg mL -1 to 100 ng mL -1 , and a superior limit of detection (LOD) as low as 0.24 pg mL -1 . It was successfully used to determine FGF-21 concentrations in serum samples and achieved satisfactory results, indicating great potential applications in clinical diagnostics.