Objective To investigate the effect of bear bile powder (BBP) and ursodeoxycholic acid (UDCA) on preneoplastic lesions of hepatocarcinoma, we conducted anticancer efficacy experiments of BBP and UDCA using short-term carcinogenesis bioassay models. Methods Forty 6-week-old male SD rats were randomly divided into control, DEN, DEN+BBP (200 mg/kg), and DEN+UDCA (30 mg/kg) groups. At the beginning of the experiment, except for the control group, all rats were injected intraperitoneally with 100 mg/kg DEN once a week for three weeks. Additionally, all rats of the last two groups were orally administered 200 mg/kg BBP or 30 mg/kg UDCA suspended solution daily from the beginning to the end of the experiment. Results In the body and liver weights, there were no significant differences between DEN, DEN+BBP and DEN+UDCA groups. The accumulation of MDA was increased by DEN treatment while the activities of SOD, GSH were decreased in the liver tissue. However, the activities of SOD, GSH were enhanced with UDCA administration, while the accumulations of MDA was decreased in the liver tissue. Contrary, BBP exerted these antioxidant effects in serum. Meanwhile, the number and area of GST-P positive lesions and Ki-67 positive cell ratio in the DEN+BBP and DEN+UDCA groups were significantly lower than those in the DEN group, and more obvious in DEN+UDCA group. In addition, the mRNA expression level of Caespase-9 was significantly increased by UDCA treatment than that of the model group. Conclusion These results suggested that 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. However, their antioxidant mechanisms are different. In addition, further research is needed to determine whether the antioxidant effect is involved in their anticancer mechanisms.