We have demonstrated that the truncated hepatitis C (HCV) core protein with its C-terminal hydrophobic domains deleted is translocated to the nucleus of transfected cells (22). In this study, intact and truncated core proteins of HCV were transiently expressed in a human hepatoblastoma cell line, HepG2, and their effects on the expression of the chloramphenycol acethyl transferase (CAT) gene driven by viral and cellular promoters were examined. The intact core protein of 22 kDa which is localized in the cytoplasm of the transfected cells suppressed the expression in all of the promoters tested. They were promoters of the SV40 early region, the c-fos oncogene, the retinoblastoma susceptibility gene, the beta-interferon gene and the beta-actin gene. In contrast, the truncated HCV core protein located in the nucleus did not show such a suppressive activity. The HCV core protein appears to function not only as a viral structural protein but as a regulator of gene expression and it might act as a suppressive factor for the cellular gene expression.