In this work, an enzyme-free electrochemical immunosensor based on metal-organic framework (MOF) and single-wall carbon nanotube (SWCN) nanocomposite coated glassy carbon electrode (GCE) for rapid and sensitive detection of fibroblast growth factor 21 (FGF-21) was proposed. The synthesized MOF/SWCN were characterized by transmission electron microscopy (TEM). It exhibited high-speed charge mobility, excellent conductivity and high surface area, significantly amplifying the current signal response. Furthermore, to immobilize the FGF-21 capture antibody on the MOF/SWCN electrode surface in an ordered orientation, staphylococcal protein A (SPA) was introduced as a connecting element, which significantly increased the antigen-binding ability and immunosensor stability. Under optimal conditions, the wide linear range of the immunosensor was 1.00 pg mL -1 to 500 ng mL -1 , with a low detection limit was 0.35 pg mL -1 . Additionally, the immunosensor also showed excellent reproducibility and selectivity. It was also successfully used to detect FGF-21 in human serum samples with satisfying recoveries. Thus, the strategy provides a simple and sensitive method for FGF-21 detection, indicating significant potential applications in clinical diagnostics.