OBJECTIVE To evaluate the effect of combination of eicosapentaenoic acid (EPA) and The effects of EPA and epirubicin (EPI) on the human gastric carcinoma cell MGC-803 in vitro. METHODS EPI were measured by MTT assay , and the interaction between these two agents was evaluated by the isobologram technique of Berenbaum. Morphous of cell was observed by phase-contrast and electron microscope. Flow cytometry was used for cell cycle analysis. RESULTS EPA significantly inhibited the growth of MGC-803 cells in a dose- and time-dependent way (P < 0.01). Numerous abnormal particles were found around the nucleus of MGC-803 cells under phase-contrast microscope, and also many electron-dense material in cytoplasm were found under electron microscope. EPA significantly stimulated the growth of human embryonal pulmonary fibroblast (HPF) dose-dependently (P < 0.01). A strong synergism was found between EPA and EPI in MGC-803 cells. EPA induced G0/G1-phase arrest but without statistical significance (P > 0.05), and EPI significantly induced S-phase arrest (P < 0.05) in MGC-803 cells. CONCLUSIONS EPA can inhibit cell growth in gastric carcinoma cells but not in normal cells. EPA and EPI have synergetic effect in the inhibition of gastric carcinoma cells. Compared with EPI monotherapy, the combination of EPI and EPA can reduce the dosage of EPI.