This study was designed to explore the mechanism of Huaier anticancer effects on experimental hepatocellular cancer (HCC) development. Seventy five rats were divided into 5 groups, administered N-nitrosodiethylamine (groups B, C, D and E) or natural saline (group A). Rats in group C and E were also given Huaier. At the 15 week sacrifice point, the HCC incidence of group C was lower than group correlating with serum AFP. The serum ALT concentration (98.9% greater) and P53 mRNA levels (23.2% ) were higher in Group B than group C. Longer term survival rates between group D and E were not significantly different. Huaier can protect liver from chemical injury and furthermore HCC development, possibly with involvement of down-regulation of P53.