Background: Infertility is a major public health and social problem in human reproduction that is known as a multifactorial complex disorder. Genetic background and mutations and single nucleotide polymorphisms (SNPs) on the genes involved in sperm development are the important causes of male infertility. Objectives: In this study, we evaluated the association of AURKC gene polymorphism (rs58264281) and idiopathic male infertility in the Iranian Azeri population. Methods: This study was performed among 100 men with idiopathic infertility (case group) and 100 healthy men with successful fertility (control group) from East Azerbaijan, Iran. Genomic DNA extraction was carried out from peripheral blood samples by the proteinase K method. Genotype analysis was conducted by the tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS PCR). SPSS version 21 was used for the analysis of the obtained data. Results: We observed that the CA and AA genotypes were significantly increased in patients with infertility as compared to healthy controls. Our results demonstrated that the mutant allele of AURKC gene polymorphism (rs58264281) was a significant risk factor in male infertility. Conclusions: We suggested a significant correlation between the AURKC gene rs58264281 polymorphism and male infertility in the Iranian Azeri population. However, further studies are required among other ethnicities, races, and geographic areas with larger sample sizes.