Objective(s): Resveratrol (RSV) is a naturally occurring plant polyphenol with cardioprotective, neuroprotective, immunoregulatory, and anticancer properties and is biologically effective against various diseases. This study aimed to investigate the chemopreventive effect of different doses of RSV against hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) in rats.Materials and Methods: The rats were randomly divided into six groups of seven rats each (n=42). The control group (group 1) was injected with saline, group 2 with dimethyl sulfoxide (DMSO), group 3 with DEN, group 4 with DEN and 50 mg/kg of RSV (DEN+RSV 50), group 5 with DEN and 75 mg/kg of RSV (DEN+RSV 75), and group 6 with DEN and 100 mg/kg of RSV (DEN+RSV 100). Pro-apoptotic Bax/anti-apoptotic Bcl-2 and tumor suppressor p53 markers were analyzed by immunostaining.Results: Superoxide dismutase, glutathione, and malondialdehyde concentrations were not statistically significant in DEN+RSV 100 group but were closest to the concentrations in control group. Liver function tests showed that enzyme activity (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transferase) increased in DEN+RSV 50 and DEN+RSV 100 groups compared with control group but decreased in DEN+RSV 50 and DEN+RSV 100 groups compared with DEN group. Bax/Bcl-2 and p53 analysis showed a statistically significant increase in apoptotic cells in DEN+RSV 100 group.Conclusion: A 100 mg/kg dose of RSV may be a promising treatment for HCC.