Objective Bear bile powder (BBP), a natural Traditional Chinese medicine (TCM), has antioxidant and anticancer effects. To clarify the modification effect of bear bile powder (BBP) on early period of hepatocarcinoma formation, we conducted an anticancer efficacy experiment using short-term carcinogenesis bioassay models. Method Forty 5-week-old male SD rats were divided randomly into the following 4 groups with 10 animals per group: DEN alone, DEN+PBO, DEN+PBO+BBP-L (200mg/kg BBP), DEN+PBO+BBP-H (400mg/kg BBP). All rats were injected intraperitoneally with 200 mg/kg N-diethylnitrosamine (DEN) and three groups given a diet containing 0.5% piperonyl butoxide (PBO). In addition, the rats of last two groups were orally administered 200 or 400 mg/kg BBP for 8 weeks. Results The relative and absolute liver weights in PBO-treated groups significantly increased compared to DEN alone group. However, the number and area of GST-P+ foci were significantly decreased in only DEN+PBO+BBP-L group compared to DEN+PBO group. In addition, the Ki-67+ cell ratio which are significantly increased by DEN and PBO were significantly decreased after treatment with BBP in both BBP-treated groups. Interestingly, the mRNA levels of Ccne1, Cdkn1b related to cell cycle Caspase 8 and Caspase 9 related to apoptosis were significantly increased only in the BBP-H group. However, these changes were not observed in the BBP-L group. Conclusion These results indicated that BBP has a suppressive effect in the early period of hepatocarcinoma formation, leading to the inhibition of preneoplastic lesions. In addition, these results suggested that the suppression mechanism of BBP is strongly involved in the inhibition of cell proliferation activity and induction of apoptosis. Furthermore, that a high dose of BBP may influence BBP’s inhibitory effect on the preneoplastic lesions.