Background: Among Egyptian females, hepatocellular carcinoma (HCC) ranks sixth, while among males it ranks second. The X-ray repair crosscomplementing group1 (XRCC1) could play a crucial role in reparation of oxidative DNA damage. An association was revealed between the risk of HCC and the genotypes and allele distribution of XRCC1 variants. Objectives: This research aimed at the evaluation of the relationship between XRCC1 gene polymorphism and the development of HCC among Egyptian patients who had HCV related cirrhosis. Patients and methods: This study recruited 93 individuals, including 31 apparently healthy subjects taken as controls (Group I), 31 cirrhotic patients with chronic hepatitis C virus (HCV) infection (Group II), and 31 HCC patients with HCV related cirrhosis (Group III). Xrcc1 gene polymorphism c.1517 G>C was determined using Polymerase Chain Reaction-Restricted Fragment Length Polymorphism (PCR-RFLP). Results: CC genotype was significantly increased (p=0.04) among HCC patients with HCV related cirrhosis (48.4%) compared to controls (12.9%). Also, C allele was significantly higher (p=0.01) among HCC patients (59.7%) compared to both cirrhotic patients (41.9%) and controls (33.9%). HCC patients had CC genotype 5.83 times more when compared to controls (OR=5.83, 95% CI= 1.46-23.3). HCC patients had C allele 2.89 times more when compared to controls (OR= 2.89, 95% CI= 1.39-6). The frequencies of (GC+CC) genotypes when combined were higher in HCC patients (71%) compared to both cirrhotic patients (58.1%) and controls (54.8%). Conclusion: The polymorphism of XRCC1 c.1517G>C was found to be associated with increased risk of HCC among patients with HCV related cirrhosis, besides; C allele had higher risk of HCC.