Abstract The study of genetic alterations that alter genes that regulate normal cellular processes, providing growth advantages and metastatic capabilities to tumor cells is fundamental for a deeper understanding of the molecular nature of different types of cancer, while revealing new therapeutic targets. The NDRG1 gene encodes a protein whose expression has been associated with tumor development and progression, but data on different types of cancer are still dubious and controversial. In order to establish a possible relationship of NDRG1 gene polymorphisms with susceptibility, clinical characteristics and evolution of patients with thyroid tumors, we undertook a comprehensive bioinformatics investigation using a series of in silico tools. We demonstrate that NDRG1 rs201348291 and rs151322132 SNPs are potential and important candidates that can influence the process of pathological development of neoplasms, including thyroid neoplasms. Further validation on thyroid nodule patients and functional studies may confirm their clinical utility in the management of these patients.