To investigate the possible antitumor activity of ginger extract against hepatic carcinogenesis initiated by diethylnitrosoamines (DEN) and promoted by carbon tetrachloride (CCl4). A total of 60 male Wistar albino rats were divided into four groups with 15 animals in each group. Rats in group 1 (control group) received a single intraperitoneal (i.p.) injection of normal saline. Animals in group 2 were given ginger (50 mg/kg/day) in drinking water for 8 weeks. Rats in group 3 (DEN group) were injected with a single dose of DEN (200 mg/kg, i.p.), 2 weeks later received a single dose of CCl4 (2 mL/kg i.g) by gavage as 1:1 dilution in corn oil. Animals in group 4 (DEN-ginger group) received the same carcinogenesis induction protocol as in group 3 plus ginger (50 mg/kg/day) in drinking water for 2 weeks before induction of hepatocarcinogenesis and continued throughout the experimental period. DEN-initiated and CCl4-promoted hepatocarcinogenesis in male Wistar rats was manifested biochemically by elevation of serum hepatic tumor markers tested; a-fetoprotein and carcinoembryonic antigen. In addition, hepatocarcinogenesis was further confirmed by a significant increase in hepatic tissue growth factors; vascular endothelial growth factor, basic fibroblast growth factor, and hydroxyproline content. A marked decrease in endostatin and metallothonein were also observed. Long-term ginger extract administration 2 weeks before induction of hepatocarcinogenesis and throughout the experimental period prevented the decrease of the hepatic content of metallothionein and endostatin and the increase in the growth factors induced by the carcinogen. Moreover, ginger extract normalize serum hepatic tumor markers. Histopathological examination of liver tissue also correlated with the biochemical observations. These findings suggest a protective effect of ginger extract against premalignant stages of liver cancer in the DEN-initiated and CCl4-promoted hepatocarcinogenesis model in rats.