OBJECTIVE The chemopreventive potential of Tephrosia purpurea extract (TPE) on N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma (HCC) in Wistar rats was assessed. METHODS HCC was induced by a single intraperitoneal injection of NDEA (200 mg/kg) followed by subcutaneous injections of CCl(4) (3 ml/kg per week) for six weeks. After administration of the carcinogen, 200 and 400 mg/kg TPE were administered orally once a day throughout the study. RESULTS The levels of liver cancer markers, including α-fetoprotein and carcinoembryonic antigen, were substantially increased by NDEA treatment. TPE treatment significantly reduced liver injury and restored the entire liver cancer markers. Additionally, TPE markedly normalized the activity of antioxidant enzymes, namely lipid peroxidation, reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase in the liver of NDEA-treated rats. Treatment with TPE significantly reduced the nodule incidence and multiplicity in the carcinogen-bearing rats. Histological observations of the liver tissues correlated with the biochemical observations. CONCLUSIONS These findings powerfully support that T. purpurea prevented lipid peroxidation, suppressed the tumour burden, and promoted enzymatic and nonenzymatic antioxidant defence systems during NDEA-induced hepatocarcinogenesis. This might have been due to modulating the antioxidant defence status, which contributed to its anticarcinogenic potential.