The interleukin (IL)-24/melanoma differentiation associated gene-7 (mda-7) is a member of the IL-10 cytokine family. Introduction of the IL-24 gene into a variety of cancer cells suppresses their growth. It has not been shown, however, whether IL-24 can suppress the growth of hepatoma cells. The purpose of this study was to determine whether the mouse (m)IL-24 gene would suppress hepatoma cells in vivo after being delivered via intramuscular electroporation. After mice were given a subcutaneous dorsal injection of ML-1 hepatoma cells, the mIL-24 gene was delivered and suppressed tumor growth. On day 140, 60% of the mIL-24-treated mice (n=10) and 0% (n=10) of the untreated control mice had survived. We also generated a mouse-hepatoma model by injecting ML-1 cells into the spleen, which resulted in tumor metastasis in the liver. Intramuscular electroporation of mIL-24 also inhibited hepatoma-cell growth in the liver. On day 50, 90% of the experimental mice (n=10) and 40% (n=10) of the control mice had survived. Liver tumors in surviving experimental mice were 50% smaller than those in control mice. IL-24 also inhibited tumor vascularization. These results suggest that IL-24 has potential therapeutic value for hepatoma