BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. The long- term survival rate of patients with HCC after prevention and management remains unsatisfactory. In order to pro- vide a novel strategy to cure HCC, we investigated the effects of antisense oligonucleotides of PKC-α on prolifera- tion and apoptosis of human hepatoma cell line HepG2 in vitro. METHODS: The human hepatocellular carcinoma cell line HepG2 was cultured and subcultured in RPMI1640 medium in vitro. PKC-α antisense oligonucleotides (asODN) of dif- ferent concentrations with a random sequence as a control were transfected into HepG2 cells by lipofectin ( LP). The cell growth index ( GI) and the clone formation rate of HepG2 were detected by MTT colorimetric assay and soft agar assay, respectively. The apoptosis rate of HepG2 treat- ed with PKC-α asODN was assayed by flow cytometry (FCM). The results were analyzed by SPSS 10.0 software. RESULTS: The GI of HepG2 transfected by PKC-α asODN with concentrations ranging from 0.10 μmol to 1.00 μmol were lower significantly than those of control groups (P < 0.05). The clone formation rates of HepG2 transfected by PKC-α asODN from 0.05 μmol to 1.00 μmol were lower significantly than those of the control groups (P < 0.01), and there was a dose-dependent relationship among them. The apoptosis rates of HepG2 treated with PKC-α asODN from 0.50 μmol to 1.00 μmol were significantly higher than those of the control groups. CONCLUSION: PKC-α asODN could inhibit the growth and proliferation of HepG2 and induce its apoptosis byblocking the cell signal transduction related to PKC-α in vitro, and may be potentially used in the prevention and management of recurrent and metastatic HCC.