Staphylococcus aureus (S. aureus) is an important cause of foodborne illness in humans and animals. In some Asian countries, Perilla (Perilla frutescens) is widely used for cooking and medicinal purposes. The current study reports its antibacterial activity against S. aureus. PEO exhibited significant antibacterial activity against S. aureus with MIC values ranged from 1 to 2 mg/ml. Growth curve illustrated that PEO had time and concentration-dependent antibacterial effects against S. aureus. The results of this study showed that PEO exerted the inhibitory effect on S. aureus through cell membrane permeabilization which was associated with generalized membrane-disrupting effects, and this corresponded to a simultaneous loss of 260-nm absorbing materials. FCM assay also demonstrated that PEO treatment markedly damaged the membrane of S. aureus. Moreover, the SEM and TEM observations also support the above hypothesis, and strongly indicated the membrane-destructing activity of PEO. This study may contribute to the effective application of PEO as a natural antibacterial agent to control foodborne pathogens in food industries., 0 Web of Conferences