The hepatic stimulator substance (HSS) was partially purified from schedule-lighted weanling rat livers. The effects of HSS on p21(ras) expression of human hepatic carcinoma cell BEL-7402 were examined. The results showed: (1) HSS was capable of promoting the proliferation of the cells, and its molecular weight was 14 20 kD; (2) the p21(ras) expression was increased under HSS effect time-dependently, and the effect of HSS appeared synergistic with EGF; (3) the p21(ras) expression induced by HSS manifested a dose-dependent manner, and the saturation effect of HSS occurred at the concentration of 100 microgram/ml. Considering together with our previous report about HSS regulation on EGF receptor, these results strongly suggest that the proliferatory effect of HSS on hepatic carcinoma cells is presumedly related with EGF receptor-mediated signal transduction.