Objective: To investigate the cellular and molecular mechanism of docosahexaenoic acid (DHA) induces apoptosis and inhibits invasion ofhepatoma cells.Methods: The time-and dose-dependent effect of DHA on the proliferative activity of hepatocellular carcinoma (HCC) cell lines SMMC-7721 and Bel-7402 were assessed by using the MTT staining method, and cell viability was estimated using the Trypan blue dye exclusion assay.Quantitation of apoptotic cells under different concentration of DHA-intake conditions was obtained by flow cytometric analysis.The expression ofbim gene was selected for qRT-PCR analysis.We detected the level of the antiapoptotic protein Bcl-2 and proapoptotic proteins Bax by Western blotting assays.Measurement of of caspase-3 activity was detected.Cell invasion and migration assays were measured by transwell and wound scratch assay.Immunohistochemisty and Gelatin zymography were employed to determine the expression of MMP-9 in HCC cells which pretreated with different concentrations of DHA for 48 h.