This study was conducted to explore the novel anticancer compounds from Chinese herbs. During the process of screening, to evaluate the potential chemopreventive effect of natural compounds, Xanthoxyletin was isolated from Erythrina variegata. It has been reported that Xanthoxyletin possesses antibacterial, fungicidal, and algicidal properties. In this study, we examined the antiproliferative effects of Xanthoxyletin against SGC-7901 cells and its ability to induce apoptosis and cell cycle arrest for the first time. We observed that its inhibitory effects on cells were associated with the DNA damage, apoptosis through mitochondrial dysfunction, and cell cycle arrest at S phase in a dose-dependent manner. Additionally, Xanthoxyletin also increased the production of reactive oxygen species in SGC-7901 cells. These results suggest that Xanthoxyletin may be promising anticancer agent and has worth for further mechanistic and therapeutic studies against gastric cancer.