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Hepatocellular carcinoma (HCC) is one of most frequent cancer in the world, genetic polymorphisms have been reported to play a role in susceptibility to HCC. The present study aimed to study the possible association between glutathione -- S -- transferase (GSTP1) gene polymorphism and susceptibility to HCC. The study was carried out on 120 subjects divided into 3 groups : Group (A) included 60 HCC patients and group (B) included 40 chronic hepatitis C virus patients and group (C) included 20 age and sex matched healthy control. All subjects were submitted to full history taking, liver function tests, GSTP1 gene polymorphism by PCR -- RFLP. This study found a significant difference between HCC group and each of hepatitis C virus group ( HCV) and control group, while there is no significant differences between HCV group and the control group as regarding GSTP1 genotyping with the highest percent of ile/val polymorphism (IV) and val/val polymorphism (VV) in HCC group and ile/ile (II) polymorphism among HCV and the control group. GSTP1 IV genotype frequency was associated with 5.53 times higher risk of HCC than GSTP1 II genotype, while GSTP1 VV genotype frequency was associated with 6.40 times higher risk of HCC than GSTP1 II genotype when compared to the other two groups together. The frequency of GSTP1 val (V) allele is higher in HCC when compared to the other two groups together and it was associated with 2.70 times higher risk of HCC than GSTP1 I allele. The present study reported that carriage of GSTP1 ile/val and val/val genotypes have a role in susceptibility to HCC and this susceptibility are not through the alteration of the expression of clinical pathological markers and we recommend performance of this work on a large scale to confirm these results. [ABSTRACT FROM AUTHOR]