Background/Aim: Oxidative stress plays a role on the development of colorectal cancer. Manganese superoxide disnzutase (MnSOD) and glutathione peroxidase I (GPXI) are crucial in regulating oxidative balance and its stabilization. Possible mechanisms of action of these enzymes in various types of cancers require further investigation. We aimed to determine expression levels of these genes and their effects on protein levels in serum of patients with colorectal cancer. Materials and Methods: Expression levels of genes were determined using Real Time-Polymerase chain reaction in 35 patients with colorectal cancer. We used enzyme-linked immunosorbent assay to determine MnSOD and GPXI levels. Results: We found significant differences in GPXI expression between tumor and normal tissues, with a 2-fold decrease in tumor tissues (p<0.05). However, although no significant difference was found between the expression of MnSOD gene in tumor and that in normal tissues, there was a 1.13-fold change in expression. We observed no relationship between expressions of either gene and their levels in serum. Conclusion: The GPXI gene may play a critical role in the development of colorectal cancer.