Background: Telomerase activity increases in cancer cells. Bcl-2 is an antiapoptotic factor that its concentration grows in many cancer cells including hepatocellular carcinoma cells. In this study, an attempt was made to investigate the effects of a new synthetic compound, platinum azidothymidine (Pt-AZT) on treatment of rats with Hepatocellular Carcinoma (HCC) and to compare its effects with azidothymidine (AZT) in alteration of telomerase activity and Bcl-2 concentration in HCC. Methods: Healthy adult male Wistar rats (n=100) were randomly divided into 4 groups (A, B, C, and D). Group A contained 25 healthy rats and was considered as the control group. Liver preneoplastic lesions were induced in remaining animals (n=75) using Solt-Farber resistant hepatocyte protocol. These animals were randomly allocated in groups B, C and D. Group B was negative control (untreated), groups C and D were treated by intraperitoneal injection (IP) of Pt-AZT (0.9 mg/kg/day) and AZT (0.3 mg/kg/day), respectively for 14 days. After the treatment period, telomerase activity and Bcl-2 concentration were determined in the rats’ liver. Results: No HCC was developed in group A, but tumors were present in all other groups. Telomerase activity and Bcl-2 concentration were significantly lower in group C compared to groups B (0.1590.06 vs. 0.5770.116 IU/L, p<0.001, respectively and 0.9310.388 vs. 3.940.74 ng/ml, p<0.001, respectively). Similar results were observed in comparison with group D (0.3310.06 vs. 0.5770.116 IU/L, p<0.001, respectively and 0.9310.388 vs. 2.940.594 ng/ml, respectively). There was a significant negative correlation between telomerase activity and Bcl-2 concentration only in untreated cancer group (p=0.034). Conclusion: In this study, higher anticancer activity of Pt-AZT in comparison to AZT was demonstrated. It effectively inhibits the growth of liver tumor in rats through extending apoptosis.