cancer in the world. The main risk factors associated with HCC are hepatitis B and hepatitis C viral infections and other factors that play a role in HCC development. Oxidative stress is an imbalance between production and elimination of reactive metabolites of oxygen and nitrogen, in favor of their production leading to potential damage. During oxidative stress, biologically important molecules and cells can be damaged, and this can be significant in the pathogenesis of many diseases. Reactive oxygen species (ROS) is known to activate the apoptosis of some hepatocytes and therefore contribute to inflammation, regeneration, fibrogenesis, and carcinogenesis. The enzyme generally considered to be the frontline defense against ROS is glutathione peroxidase (GPX).The present study aims to investigate the association of progression of HCC with GPX1 (Pro198Leu) gene polymorphisms in HCC Egyptian patients. One hundred HCC cases and matched 100 controls were recruited from National Cancer Institute and Kasr El-Aini respectively. The detection of the genetic polymorphisms of GPX1 (Pro198Leu) were determined by single nucleotide polymorphisms (SNPs) using real time PCR technique. The results showed that there is a significant association between the GPX1 polymorphisms and the progression of HCC, the distribution of different GPX1 polymorphisms in HCC patients infected with HCV was (47.5% CC, 47.0% CT and 81.3% TT) respectively and in controls was (52.5% CC, 53.0% CT and 18.8% TT) respectively (P=0.033). Our findings suggested that the genetic polymorphisms in GPX1 play a role in the etiology of hepatocellular carcinoma.Conclusion: AFP is highly significant in relation to HCC cases and in also with GPX1 gene mutation. Our findings suggested that the genetic polymorphisms in GPX1 play a role in the etiology of hepatocellular carcinoma.