Abstract Introduction: The concept that some dietary proteins may prevent the onset or spread of hepatocellular carcinoma (HCC) was tested in mice model in this study. Experimental procedure: The animals were divided into seven groups, with six mice in each based on diet treatment. Group I- Control, Group II- Diethylnitrosamine (DEN) alone treated, Group III- Soy protein treated, Group IV- Garlic protein treated, Group V- Coconut protein treated, Group VI- Whey protein treated, Group VII- Casein treated. The animals were acclimatized in their respective diets for 60 days. On the 60th day, DEN was given intraperitoneally as a single dose (120 mg/kg body weight) in saline, to each animal in groups from II to VII, and was followed by weekly subcutaneous injections of carbon tetrachloride for four weeks at individual doses of 3 mL/kg body weight to induce hepatocellular carcinoma. Group I and II, were continued on the normal diet and the groups III to VII were fed their respective diets for 120 days. Thus Group II consisted of animals that were HCC-induced with DEN. Animals belonging to groups III-VII were pre and post treated with different protein isolates from specific sources. At the end of the experimental period, ie. on day 120, the mice were sacrificed and blood for serum separation and liver sample for biochemical analysis were collected. Alpha-fetoprotein, ornithine decarboxylase, tumor necrosis factor-β, gamma-glutamyl transpeptidase, aspartate transaminase, alanine transaminase, alkaline phosphatase, and antioxidant enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase were assayed both in serum and in liver homogenate. Summary of data: The levels of alpha-fetoprotein, ornithine decarboxylase, tumor necrosis factor-β, gamma-glutamyl transpeptidase, aspartate transaminase, alanine transaminase and alkaline phosphatase were elevated and the antioxidant enzymes were significantly (P<0.05) decreased in diethylnitrosamine alone treated mice. The activities of marker enzymes and antioxidant enzymes were significantly (P<0.05) restored in the animals treated with various protein isolates. Histological sections of liver of DEN alone-administered group had gross structural alterations in comparision with control mice. The cytoplasmic material was compact with clear cell foci in soy protein, garlic protein and coconut protein pre and post-treated groups. In addition, the level of Immunoglobulin E (IgE) expression was estimated as a measure of allergic reaction. Garlic protein treated and whey protein treated animals had high values of IgE. Conclusions: The overall results confirm the protective role of these protein isolates. Among them the soy protein, garlic protein and coconut protein were better than others in preventing hepatocellular carcinoma like condition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1620. doi:1538-7445.AM2012-1620