SMAD7 has been identified as a functional candidate gene for colorectal cancer (CRC). SMAD7 protein isa known antagonist of the transforming growth factor beta (TGF-b) signaling pathway which is involved intumorigenesis. Polymorphisms in SMAD7 may thus alter cancer risk. The aim of this study was to investigatethe influence of a SMAD7 gene polymorphism (rs2337107) on risk of CRC and clinicopathological featuresin an Iranian population. In total, 210 subjects including 105 patients with colorectal cancer and 105 healthycontrols were recruited in our study. All samples were genotyped by TaqMan assay via an ABI 7500 Real TimePCR System (Applied Biosystems) with DNA from peripheral blood. The polymorphism was statisticallyanalyzed to investigate the relationship with the risk of colorectal cancer and clinicopathological properties.Logistic regression analysis revealed that there was no significant association between rs2337107and the risk ofcolorectal cancer. In addition, no significant association between genotypes and clinicopathological features wasobserved (p value>0.05). Although there was not any association between genotypes and disorder, CT was themost common genotype in this population. This genotype prevalence was also higher in the patients with wellgrade (54.9%) and colon (72.0%) tumors. Our results provide the first evidence that this polymorphism is not apotential contributor to the risk of colorectal cancer and clinicopathological features in an Iranian population,and suggests the need of a large-scale case-control study to validate our results.