EGF receptor has been recognized to playing an important role in the regulation of normal and tumor cell growth. In this study, the transmodulatory effect of IFN gamma on EGF receptor of human hepatocellular carcinoma cell line HepG2 was investigated. The results demonstrated that IFN gamma was able to modulate EGF receptor of HepG2 cells by enhancing the tyrosine phosphorylation of the receptor. However, the effect appeared only if EGF was present, but not mediated by IFN gamma alone. No significant alteration was found in terms of the expression or the affinity of EGF receptor when HepG2 cells were treated with IFN gamma. In addition, EGF internalization in the cells was also not affected. Because IFN gamma is an inhibitory agent for the growth of HepG2 cells, this transmodulatory effect of IFN gamma on the tyrosine phosphorylation of EGF receptor might be associated with the inhibition of the growth of HepG2 cells.