Chronic hepatitis C (CHC) is a worldwide etiology of chronic hepatic insult particularly in Egypt. DNA‐repair systems are responsible for maintaining genomic integrity by countering threats posed by DNA lesions. Deficiency in the repair capacity due to genetic alterations in DNA‐repair genes can lead to genomic instability and increased risk of cancer development. The present work aimed at studying the possible association between XRCC1‐G28152A (rs25487), XRCC3‐C18067T (rs861539), and XRCC7‐G6721T (rs7003908) single nucleotide polymorphisms (SNPs) and the susceptibility to hepatocellular carcinoma (HCC) in Egyptian population. The study was conducted on 100 newly diagnosed HCC patients and 100 age‐ and sex‐matched healthy controls. Laboratory workup revealed that all HCC patients have chronic hepatitis C viral infection. Genotyping of the studied SNPs was performed by real‐time PCR. The heteromutant genotype of XRCC1 (GA) conferred an almost two‐fold increased risk of HCC (OR ,  2.35; 95% CI, 1.33‐4.04). Regarding XRCC7, the heteromutant (TG) genotype conferred a two‐fold increased risk of HCC (OR ,  2.17; 95% CI, 1.23‐3.82). Coinheritance of the polymorphic genotypes of XRCC1 and 7 was significantly higher in HCC cases than controls and was associated with an 11‐fold increased risk of HCC (OR , 11.66; 95% CI,  2.77‐49.13). The frequency of XRCC3 polymorphic genotypes in HCC patients was close to that of the controls.