Abstract The present study aimed to early investigation of hepatocarcinogenic effect of poly vinyl chloride on male albino rats in order to improve cancer therapy through studying the toxic effect of PVC on some biochemical changes as ALT, AST, ALP and alfa-fetoprotein as tumor marker. Also study the changes in m-RNA expression of cytochrome P450 2E1 (CYP2E1) and tumor suppressor gene (TP53) as early cancer biomarker. Sixty male albino rats used in this study and classified to 3 groups: Group I used as control, while Group II (1/20 LD50 of PVC) and Group III (1/10 LD50 of PVC) were given PVC orally via stomach tube three times per week for 2 months. The results were more pronounced on increase of some biochemical parameter (ALT, AST, ALP and alfa fetoprotein) and m-RNA expression of tumor suppressor gene (TP 53) at the first and second month of the experiment. Also found an increase of m-RNA expression of cytochrome2E1 gene (CYP2E1) at first month and decrease at second month. This study provided strong evidence that application of gene expression profiling to preneoplastic liver diseases and hepatocellular carcinoma is particularly important in early investigation of carcinogenic risk by toxic agent like PVC. -Keywords: Poly vinyl chloride, Hepatocellular carcinoma, gene expression, Alfa fetoprotein.