Objective To observe the effects of oxaliplatin on proliferation in human hepatoma cell lines QGY in vitro and investigate the mechanism. To provide the theory foundation whether it can be used for the chemotherapy of hepatocellular carcinoma. Methods The inhibition of proliferation in QGY cell was estimated by MTT-test. Morphologic changes were observed under light microscope and electronic microscope. Distribution of cell cycle and apoptosis was analyzed using flow cytometry. The expression of cell cycle protein and apoptosis-associated gene protein was detected with immunohistochemical technique. Results Oxaliplatin could inhibit the proliferation of QGY cells and the inhibition depended on the exposure time and dose. The cells showed morphologic changes at the early stage of apoptosis under the light microscope: the shrunk and round cells, condensed cytoplasma and pycnosis nucleus. Apoptotic cells and apoptotic body could be found under the transmission electronic microscope. The analysis of cell cycle indicated that oxaliplatin blocked cells at S and G_2/M phases and the cells of G_0/G_1 phase reduced. When treated with oxaliplatin for 72 h, the expression of cyclin A and Bax were up-regulated, mutant type P53, Bcl-2 and Myc down-regulated, and Fas was not changed. Conclusion Oxaliplatin could inhibit proliferation of the hepatoma cell lines. Cell cycle blocked at S and G_2/M phase. The apoptosis were related to the up-regulation of Bax and down-regulation of mutant type P53, Bcl-2 and Myc. It could not induce apoptosis through the Fas approach.