OBJECTIVE: To investigate the effect of omega-3 polyunsaturated fatty acids(omega-3PUFAs) on the apoptosis of human gastric cancer cell line SGC-7901 and to explore the potential mechanisms. METHODS: Cells were treated with eicosapentaenoic acid (20:5omega-3,EPA) or docosahexaenoic acid (22:6omega-3, DHA) at concentrations of 10, 20 and 40 mug/ml. Cell growth and apoptosis were analyzed with MTT assay, cell morphology, DNA electrophoresis and flow cytometry. Mitochondrial membrane potential ( triangle right psi mt) was measured by fluorescent probe rhodamine 123. The distribution of cytochrome C in mitochondria and cytosol was determined by enzyme-linked immunoadsorbent assay. The composition of mitochondrial membrane phosphlipid(MMP)was examined by gas chromatography. RESULTS: Both EPA and DHA markedly inhibited the SGC-7901 cell growth and induced apoptosis in a time- and dose-dependent manner. After incubation of the cells with 40 mug/ml EPA or DHA for 24 hours, the level of triangle rightpsimt siginificantly decreased (P<0.001), and cytochrome C largely released into cytosol from mitochondria. The proportions of EPA and DHA in MMP rapidly elevated while that of arachidonic acid sharply decreased. CONCLUSIONS: omega-3PUFAs inhibit the growth of gastric cancer cells through promoting apoptosis. Compositional and functional alterations in mitochondrial membrane may be an important initiator of apoptosis induced by omega-3PUFAs.