VraX is a protein secreted by Staphylococcus aureus, an important human pathogen. A dramatic over expression of VraX is observed when S. aureus is exposed to several antimicrobial agents; however, its function remains unclear. Here, we aimed to reveal the function of this protein and the mechanism by which it affects the immune system to enhance the pathogenesis of the bacterium. Our results showed that VraX specifically inhibited the classical pathway of the complement system. In particular, VraX could bind to the C1q protein and block the formation of the C1 complex. Deletion of VraX decreased the pathogenesis of S. aureus. Our findings indicate that over expression of VraX might be a protective response for S. aureus survival.