Abstract Background Infertility is defined as the inability to get pregnant during 12 months or more regular unprotected sexual intercourse. Fertility is initiated by hormonal signals from brain to the gonads which lead to leakage of gonadotropin hormones. Recently, Kisspeptin (Kp) and its receptor have been identified as vital upstream regulators, integrating central and environmental signals through gonadotropin-releasing hormone. Aim of the study In this study, the relationship between rs397515615 polymorphism of KISS1R gene and idiopathic male infertility was investigated in Guilan population. Patients and methods In this study, the samples from 50 infertile men and 50 healthy men (as controls) were tested. Allele specific polymerase chain reaction method was applied for determination of the codon 56 (rs397515615) polymorphism. To estimate the association between genotype and allele frequencies in cases and controls, P-values were assessed by chi-square (χ 2 ) analysis. Results and conclusion Results showed that genotype frequencies had significant differences between control and patient groups (P = 0.02) while the distribution of alleles (Gly/Ala) was not significant (P = 0.20). The results, revealed that rs397515615 polymorphism of KISS1R gene increases susceptibility to idiopathic male infertility. However, future studies with large scale and different geographical population need to confirm our results.