Objective To investigate the effect of bear bile powder (BBP) and ursodeoxycholic acid (UDCA) on preneoplastic lesions of hepatocarcinoma, using short-term carcinogenesis bioassay models. Methods Forty 6-week-old male SD rats were divided randomly into control, diethylnitrosamine (DEN), DEN + BBP (200 mg/kg), and DEN + UDCA (30 mg/kg) groups. All rats, except for the control group, were injected intraperitoneally with 100 mg/kg DEN once a week for 3 weeks. Rats in the DEN + BBP and DEN + UDCA groups also received oral BBP 200 mg/kg or UDCA 30 mg/kg suspended solution, respectively, daily from the beginning to the end of the experiment. Results There were no significant differences in body or liver weights between the DEN, DEN + BBP, and DEN + UDCA groups. DEN treatment increased the accumulation of malondialdehyde (MDA), decreased superoxide dismutase (SOD), and reduced glutathione (GSH) activities in liver tissue, while UDCA enhanced SOD and GSH activities and decreased MDA accumulation in liver tissue. In contrast, BBP exerted these antioxidant effects in serum. The number and area of glutathione S-transferase placental(GST-P) type-positive lesions and the Ki-67-positive cell ratio were significantly lower in the DEN + BBP and DEN + UDCA groups than in the DEN group, especially in the DEN + UDCA group. UDCA significantly increased Caspase-9 mRNA expression compared with the model group. Conclusions BBP and UDCA have significant inhibitory effects on preneoplastic lesions of hepatocarcinoma induced by DEN, and both have antioxidant effects on DEN-induced oxidative stress. The antioxidant mechanisms of BBP and UDCA differ, however, and further research is needed to determine the roles of the antioxidant effects in their anticancer mechanisms.