Abstract: OBJECTIVE To study the anti-tumor effect of genistein(GEN) MePEG-PLGA copolymer micelles on human hepatoma SMMC-7721 cells in vitro and in vivo. METHODS MTT assay, Annexin V-FITC/PI staining were used to investigate the effects of GEN MePEG-PLGA copolymer micelles on cytotoxicity, apoptosis and cell cycle of human hepatoma SMMC-7721 cells. The in vivo anti-tumor effect of GEN micelles was investigated in nude mice bearing hepatocellular carcinoma SMMC-7721 tumor in vivo. RESULTS The inhibitory rate of GEN micelles in SMMC-7721 cells were higher than GEN and the highest inhibition rates were 83.26% and 78.25%, respectively. The results of flow cytometry showed that the GEN micelles group could increase the ability of GEN to induce apoptosis of SMMC-7721 cells and presented a concentrationdependent manner. When the concentration of 5, 10, 20 μg·mL^-1 GEN and GEN micelles groups acted on SMMC-7721 cells for 48 h, the GEN micelles could significantly enhance the ability of arrest cell in G₂/M phase for GEN, and showing a concentration-dependent manner. In vivo anti-solid tumor experimental results showed that the same concentration of GEN micelles group had significantly better anti-tumor effect than GEN emulsion, and in a concentration-dependent manner, the highest tumor inhibition rate was 55.41%. CONCLUSION The GEN MePEG-PLGA copolymer micelles has significant anti-hepatocarcinoma effects both in vivo and in vitro.