<i>Objective:</i> We examined the growth-inhibitory effect and the mechanism of action of type I interferon (IFN) in human liver cancer cell lines in vitro and in vivo. <i>Methods:</i> We examined the growth-inhibitory effect of 5 types of type I IFN preparations (e.g., pegylated, nonpegylated IFN-α, and IFN-β) used for the treatment of chronic hepatitis C in 13 liver cancer cell lines in vitro. After liver cancer cells were transplanted into nude mice, various doses of IFN preparations were subcutaneously administered, and the antitumor effect was examined. <i>Results:</i> The growth-inhibitory effect of each preparation was different, but IFN-β expressed the strongest effects in vitro. Induction of an inhibition of cell cycle progression at the G<sub>1</sub>, S or G<sub>2</sub>/M phase with or without apoptosis was the mechanism of action of IFN. IFN preparations induced a dose-dependent decrease in tumor volume and weight by inducing tumor cell apoptosis in vivo, and tumor growth was effectively suppressed even at the clinical dose for chronic hepatitis C treatment. The antitumor effect of pegylated IFN was significantl
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