Gastrointestinal (GI) cancers are known to have a high incidence worldwide and require an early diagnosis to successfully treat them, providing higher survival rates and better quality of life for the patients. MicroRNA-27a is a well-known oncogene that plays a significant role in various GI cancers. It is known to upregulate the expression of numerous oncogenes leading to cancer progression. The miR-27a harbors two polymorphisms rs895819 and rs11671784 which alter the disease susceptibility by interfering with the maturation and expression of miR-27a. In the current study, we aimed to investigate the role played by these polymorphisms in cancers of the GI tract. We conducted a case-control study with 210 GI cancer cases and 210 cancer-free controls to analyze the effect of these polymorphisms. The rs895819 polymorphism was genotyped using PCR-RFLP, and rs11671784 was genotyped on a MassARRAY platform. The association analysis failed to bring out any significant association of the polymorphisms with GI cancer risk. However, genotype-phenotype interaction analysis revealed that the rs895819 was found to increase the risk GI cancers along with the presence of risk factors such as socioeconomic status, diabetes mellitus, hypertension, alcohol consumption, and tobacco chewing. © 2020 Cancer research; Genetics; Oncology; Gene Mutation; Gene Regulation; Genomics; Polymerase Chain Reaction; Biochemistry; Molecular Biology; Pathophysiology; Epidemiology; miR-27a; rs895819; rs11671784; Gastrointestinal cancers; MassARRAY, PCR-RFLP © 2020