Colorectal cancer (CRC) is the third most common malignancy worldwide. DNA damage that contributes to carcinogenesis is normally corrected by the specific DNA repair pathways which reduces genomic instability and carcinogenesis risk, through removal of damaged DNA. The aim of the study was to assess the Association of DNA repair gene variants XRCC1 c. 1196 A>C and MLH1 −93G>A & c. 655A>G with CRC susceptibility in a sample of Egyptian patients. Methods: Eighty CRC patients and 80 apparently healthy subjects were tested for the DNA repair gene variants XRCC1 c. 1196 A>C and MLH1 −93G>A & c. 655A>G by Taqman Real-Time PCR. The results: No statistically significant association was found in the genotype distribution of the studied three variants (XRCC1 c. 1196 A>C and MLH1 −93G>A & c. 655A>G) between the CRC cases and the control group. A statistically significant association between the MLH1 −93G>A genotype and both the site of the tumor and the lymph node staging (N), a part of TNM staging, has been demonstrated with a P-value of (0.025 and 0.016), respectively. Conclusion: The results of this study suggest that the DNA repair genes variants XRCC1 c. 1196 A>C and MLH1 −93G>A & c. 655A>G have no statistically significant association with CRC in Egyptian patients