Objective Bear bile powder (BBP), a natural Traditional Chinese medicine, has antioxidant and anticancer effects. To clarify the effect of BBP on the early period of hepatocarcinoma formation, we conducted anticancer efficacy experiments using short-term carcinogenesis bioassay models. Methods Forty 5-week-old male SD rats were randomly divided into DEN-alone, DEN + PBO, DEN + PBO + BBP-L (200 mg/ kg BBP), and DEN + PBO + BBP-H (400 mg/ kg BBP) groups, with 10 animals per group. All rats were injected intraperitoneally with 200 mg/ kg DEN, and the last three groups were provided a diet containing 0. 5% PBO. Additionally, rats of the last two groups were orally administered 200 or 400 mg/ kg BBP for 8 weeks. Results The relative and absolute liver weights of PBO-treated groups were significantly increased compared with those of the DEN alone group. However, the number and area of GST-P+ foci were significantly decreased in the DEN + PBO + BBP-L group compared with the DEN + PBO group. Additionally, the Ki-67+ cell ratio was significantly increased by DEN and PBO, and significantly decreased by BBP in both BBP-treated groups. Interestingly, the mRNA levels of Ccne1 and Ccne1b related to the cell cycle and Caspase 8 and Caspase 9 related to apoptosis were significantly increased in the DEN + PBO + BBP-H group. However, these changes were not observed in the DEN + PBO + BBP-L group. Conclusions BBP has a suppressive effect on the early period of hepatocarcinoma formation, leading to inhibition of preneoplastic lesions. Additionally, the suppression mechanism of BBP involves inhibition of cell proliferation and induction of apoptosis. A high dose of BBP may influence its inhibitory effect on preneoplastic lesions.