Protective effect of Cassia fistula against N-Diethylnitrosamine (DEN) induced hepatocarcinogenesis was studied in rats. Ninety six male Wistar albino rats were randomly allotted to four groups of 24 rats each. Hepatocarcinogenesis and the protective effect of C. fistula were studied by administering 0.01% of DEN in drinking water ad libitum and C. fistula 500 mg/kg BW per os either alone or in combination for 120 days. After DEN administration, hepato to cellularpathology was observed grossly and histologically. In addition, elevated serum ALT, AST and GGT levels, hypoalbuminaemia, increased BUN and creatinine were observed in DEN treated rats. A significant (P<0.05) decrease in the CAT and SOD values was observed in the DEN and DEN+ C. fistula groups when compared to the other groups of rats. There was a significant (P<0.05) increase in the GSH, GPx and GGT values in the DEN and DEN+ C. fistula treated groups when compared to control and C. fistula groups. Liver showed significant (P<0.05) increase in lipid peroxidation values throughout the trial period. Concurrent administration of C. fistula with DEN significantly alleviated the effects of DEN on serum AST level, BUN value and relative liver weight. There was a significant (P<0.05) increase in the liver lipid peroxidation in the DEN and DEN+ C. fistula groups when compared to the other groups. It was concluded that C. fistula possess significant hepatoprotective potential against DEN induced hepatocarcinogenesis.