Background: It has been proposed that folate and polymorphisms of the enzyme methylenetetrahydrofolatereductase (MTHFR), which regulates influx of folate for methylation reactions for DNA synthesis and repair,are involved in colorectal cancer. This study was designed to determine the influence of a genetic variant (MTHFRG1793A) and folate on colon cancer in Iran. Materials and Methods: We analyzed 227 cases and 239 normalunmatched controls using pyrosequencing. Odds ratios and 95% confidence intervals (95% CI) were calculatedto evaluate associations of the MTHFR gene polymorphism with colorectal cancer risk. Results: A significantlyreduced risk of recurrence was observed in patients heterozygous for the MTHFR G1793A polymorphism (OR:0.17; 95% CI, 0.05- 0.52). The frequency of GG, GA and AA genotypes of MTHFR among the colorectal cancerpatients were 98%, 2% and 0% respectively, while the frequencies among controls were 90%, 10% and 0%,respectively. Furthermore, a significant reduction in recurrence risk was seen in MTHFR G1793A heterozygoteslimited to those who received folate supplements. Conclusion: Our study is compatible with previous findingsconcerning a reverse association between the MTHFR 1793G>A genotype with cancers in different populations.