Background: Catalase (CAT), one antioxidant enzyme, may provide resistance against many diseases. Many previous studies reported predictive and prognostic values of CAT C262T polymorphism in cancers, with divergent results. The present study was planned to assess the presence of CAT C262T polymorphisms in Egyptian patients with chronic hepatitis C virus .Methods: Genomic DNA from peripheral whole blood of 243 patients with chronic hepatitis C, of whom134 patients had hepatocellular carcinoma (HCC) and 112 healthy controls were extracted and amplified .The detection of the genetic polymorphisms of CAT C262T were determined by single nucleotide polymorphisms (SNPs) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results: The obtained results showed that, CC genotype in controls was higher than patients (HCV, HCC) in contrary with TT genotype. The results indicated that the distribution of the CC, TT genotypes were significantly different between the control and HCV group (P =0.003, 0.005 respectively), the similar results showed with HCC group in compared with control (P =0.006, 0.008 respectively).On the other hand, the CT genotype showed no significantly different between the control and the patients of HCV, HCC groups (P=0.272, 0.292 respectively. Conclusion: The CAT C262T polymorphisms may be play a role in the etiology of hepatocellular carcinoma but further studies are necessary to confirm our data.