Liver cancer represents a complex and fatal malignancy derived primarily due to oxidative stress and inflammation; it is the second most prevalent cause of death in underdeveloped and developing countries. The main objective of the present study was to investigate the hepatoprotective effect of pomegranate juice (PJ) and apple juice (AJ) against N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in male rats. Sixty adult male Sprague Dawley rats weighing 200 ± 5 g were used and randomized into 6 groups. Results showed that PJ and AJ antagonized NDEA-induced elevations of serum biochemical indices AST, ALT and ALP, and inhibited tumor biomarkers (alpha fetoprotein), TNF-α and NF-κ β and normalized the serum levels of total bilirubin, protein and albumin. The higher dose of PJ and AJ partly alleviated hepatic preneoplastic lesions induced by NDEA. The mechanistic studies revealed that PJ and AJ decreased the elevated in malondialdehyde, increased the content reduced glutathione and restored activities of SOD, GPx, and CAT antioxidant enzymes in hepatic tissue. In conclusion, PJ and AJ have a protective effect against NDEA-induced hepatocellular carcinoma.