Objective: To investigate the effect of the herb decoction Gongai Duoming Tang(GADMT) on hepatocellular carcinoma(HCC) cell line HepG2. Method: MTT was used to detect the cytotoxicity of the decoction to HepG2 and RT-PCR was used to detect the expression of hypoxia-inducible factor 1α(HIF1α) and the apoptosis-related genes Bax and Bcl-2 in HCC cell line after treated by GADMT decoction. Result: MTT demonstrated that the GADMT decoction had a strong cytotoxicity to HepG2 as much as 80% after treating the cells with 6.375 g·L-1 of concentration; the treatment also increased the expression of HIF1α promptly at 3 h and as high as 3 times at 24 h later; but the change of the Bax as well as Bcl-2 were more sophisticated. Conclusion: The GADMT decoction has a strong cytotoxic effect on HCC cell line HepG2 and the mechenism might be related with interruptting or damaging the cell respiration since a prompt increase of the expression of HIF1α. The decoction may have also an influence on the cell apoptosis.