This study investigated the effect of curcumin against diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Rats were divided into three groups. The first group served as a control. The second group received DEN (orally, 20 mg/kg) five times a week for 8 weeks, followed by 10 mg/kg for another 7 weeks. The third group was supplemented with 2% curcumin diet simultaneously with DEN. The results showed normalization of serum level of total antioxidant capacity, γ-glutamyl transferase and aminotransferase activities along with deoxyribonucleic acid, ribonucleic acid and malondialdehyde levels, glutathione reductase and glutathione peroxidase activities in the liver of curcumin group. Significant decreases in the elevated level of glutathione, glutathione-S-transferase and glucose-6-P dehydrogenase activities were observed. Serum alkaline phosphatase activity and the relative liver weight were not significantly altered. Concomitantly, the histopathological damage was attenuated by curcumin. In conclusion, curcumin exerted a potential chemopreventive effect in DEN-induced hepatocarcinogenesis.