Oxidative stress is known to be one of the major factors involved in the development and progression of cancer. Superoxide dismutase and Catalase plays an important role in the primary defence against oxidative stress. The present study was therefore undertaken to investigate the association between polymorphism of superoxide dismutase (SOD1, SOD2, SOD3) and Catalase (CAT1 & CAT2) and the gastro intestinal cancer risk in the rural population of the south western Maharashtra. The present casecontrol study included 200 confirmed gastrointestinal (GI) cancer patients and 400 age and gender matched healthy controls. The polymorphism in the Superoxide Dismutase and Catalase genes was studied out by PCR-RFLP method. When we studied the genotypic frequency of SOD1, SOD2, & SOD3, SOD2 (rs1141718) showed the negative association with the GI cancer risk [OR: 0.3097, CI: 0.1727-0.5553, p <0.0001]. There was no significant association found between SOD1 & SOD3 of superoxide dismutase and CAT1 & CAT2 of Catalase gene polymorphism and susceptibility of GI cancer. The present study shows no significant association of SOD1 (G allele of rs 2070424), SOD3 (A allele of rs2536512), CAT1 (T allele of rs7943316) and CAT2 (rs1001179) with the development of gastrointestinal cancer in the rural population of south western Maharashtra from India. However, SOD2 (rs1141718) shows the negative association with the development of GI cancer.