Following our previous finding which revealed that FV-429 induces apoptosis in human hepatocellular carcinoma HepG2 cells, in this study, we found that FV-429 could also induce apoptosis in human gastric cancer cells. Firstly, FV-429 inhibited the viability of BGC-823 and MGC-803 cells with IC50 values in the range of 38.10 ± 6.28 and 31.53 ± 6.84 µM for 24 h treatment by MTT-assay. Secondly, FV-429 induced apoptosis in BGC-823 and MGC-803 cells through the mitochondrial-mediated pathway, showing an increase in Bax/Bcl-2 ratios, and caspase-9 activation, without change in caspase-8. Further research revealed that the mitogen-activated protein kinases, including c-Jun N-terminal kinase, extracellular regulated kinase, and p38 mitogen-activated protein kinase, could be activated by FV-429-induced high level ROS. Moreover, FV-429 also promoted the ERK2 nuclear translocation, resulting in the co-translocation of p53 to the nucleus and increased transcription of p53-regulated proapoptotic genes. FV-429 significantly inhibited the nude mice xenograft tumors growth of BGC-823 or MGC-803 cells in vivo.