AbstractAim  Colorectal cancer is common, accounting for nearly 10% of all cancers. Transforming growth factor‐β1 (TGF‐β1) is a pleiotropic cytokine that has been implicated in the pathogenesis of colorectal neoplasia. The most studied −509C>T polymorphism of TGF‐β1 gene has been associated with various kinds of cancer. This study investigated the association between this genetic variant and the risk and/or progression of colorectal cancer.Method  A case–control study was carried out of 150 colorectal cancer cases and 503 healthy controls. DNA was extracted from blood cell nuclear materials, and −509C>T polymorphism in the TGF‐β1 gene promoter was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Colorectal cancer tissues (n = 70) were obtained from the studied cases for measurement of TGF‐β1 mRNA expression levels. We also assessed the plasma TGF‐β1 levels of cases (n = 88) and healthy subjects (n = 120).Results  The TGF‐β1 producer genotype, −509TT, was not associated with an increased risk of colorectal cancer compared with other genotypes. Colorectal cancer patients especially those with a more aggressive disease behaviour were more frequently associated with C allele.Conclusion  The results suggest that TGF‐β1 −509C>T polymorphism is not associated with either an increased risk or progression of colorectal cancer.