We investigated the effects of consensus interferon (IFN-αCon1), a nonnaturally occurring type I interferon with higher specific activity than other type I IFNs, on the growth of human liver cancer cells.The effect of IFN-αCon1 on the proliferation of 13 liver cancer cell lines was investigated in vitro. Hepatocellular carcinoma (HCC) cells (KIM-1 and HAK-1B) were transplanted subcutaneously into the back of nude mice, then IFN-αCon1 was subcutaneously administered to the mice once a day for 2 weeks, and tumor volume and histology were examined.IFN-αCon1 expressed a dose-dependent growth inhibitory effect in all cell lines in vitro. KIM-1 tumor volume in mice that received 0.01μg (10 4 IU)/mouse/day of IFN-αCon1 (similar to the clinical dose for chronic hepatitis C) was 62% of the control, 0.1μg/mouse/day resulted in 26%, and 1μg/mouse/day resulted in 10%. HAK-1B tumor volume under the same treatment was 61, 24 and 0% of the control, respectively. The number of apoptotic cells significantly increased and the number of blood vessels significantly decreased with the increase in IFN-αCon1 dose.IFN-αCon1 suppressed HCC growth in nude mice. These data indicate the potential clinical application of IFN-αCon1 in the prevention and treatment of HCC.