In this study, we aimed to evaluate the effect of ${alpha}$-cyperone on S. aureus. We used a hemolysin test to examine the hemolytic activity in supernatants of S. aureus cultured with increasing concentrations of ${alpha}$-cyperone. In addition, we evaluated the production of ${alpha}$-hemolysin (Hla) by Western blotting. Real-time RT-PCR was performed to test the expression of hla (the gene encoding Hla) and agr (accessory gene regulator). Furthermore, we investigated the protective effect of ${alpha}$-cyperone on Hla-induced injury of A549 lung cells by live/dead and cytotoxicity assays. We showed that in the presence of subinhibitory concentrations of ${alpha}$-cyperone, Hla production was markedly inhibited. Moreover, ${alpha}$-cyperone protected lung cells from Hla-induced injury. These findings indicate that ${alpha}$-cyperone is a promising inhibitor of Hla production by S. aureus and protects lung cells from this bacterium. Thus, ${alpha}$-cyperone may provide the basis for a new strategy to combat S. aureus pneumonia.