Objective：To prepare a monoclonal antibody against SraPL-lectin，a serine-rich repeat protein of Staphylococcus aureus，and analyze its function. Methods：The SraPL-lectin gene was amplified by PCR from USA 300 DNA，and inserted into pET28a plasmid. The pET28a- SraPL-lectin was transferred into E.coli. BL21（DE3）and induced with 0.1 mmol/L isopropyl-β-d-thiogalactoside（IPTG）for 6 h at 25 ℃. The recombinant protein was purified by His label affinity chromatography. The purified protein was used as an antigen to generate an anti-SraPL-lectin monoclonal antibody. The mAb was identified by ELISA and Western blot. A549 cells were pre-incubated monoclonal antibodies with different final concentrations. Mice were injected with 1 μg anti-SraPL-lectin monoclonal antibodies one day before challenge. The effect of adhesion and invasion was counted by plating bacteria on TSA. Results：We successfully constructed a prokaryotic expression pET28a-SraPL-lectin vector，and the SraPL-lectin recombinant protein was expressed and purified. We also generated a clone of hybridoma with SraPL-lectin binding activity，and obtained anti-SraPL-lectin monoclonal antibody purified from mouse ascites by protein G column. The titer of mAb was 1∶320 000. Pre-incubation of A549 cells with a final concentration of 100 ng/mL for 2 h significantly reduced the adherence and invasion of S. aureus on A549 cells. The number of bacteria in blood was significantly decreased when mice were administered 1 μg anti-SraPL-Lectin monoclonal antibodies. Conclusion：The anti-SraPL-Lectin monoclonal antibody prepared in this study significantly reduced the adherence and invasion of S. aureus on host cells. This study lays the foundation for the development of SraPL-Lectin as a target for the prevention and treatment of S. aureus infection in future.