The effect of thyrosine kinase, calmodulin and voltage-dependent Ca2+ channel on the proliferation of hepatoma cells induced by EGF was studied. Hepatoma cell line SMMC7721 was cultured in RPMI1640 serum-free medium. DNA synthesis rate of hepatoma cells was measured byHTdR incorporation. 10-9 mol/L EGF could significantly stimulate the proliferation of hepatoma cells (P＜0. 05), and this effect might be significantly inhibited by tyrosine kinase inhibitor (P＜0. 001).Calmodulin inhibitor W-7 had no effect on the basic phase of cultured hepatoma cells (P＞ 0. 05),but it had very significantly inhibitory effect on the proliferation of hepatoma cells induced by EGF (P＜0. 001). Voltage-dependent Caz+ channel inhibitor Varapamil had no inhibition on the proliferation of hepatoma cells induced by EGF (P＞0. 05). It had no effect on the basic phase of cultured hepatoma cells (P＞0. 05). It is suggested that tyrosine kinase and Ca2+-calmodulin-dependent pathway may play a critical role on the proliferation of heptoma cells induced by EGF, and voltage-dependent Ca2+ channel is independent of the effect of EGF.