The objective of the present study is to investigate the association between SEPT12 gene variation and the risk of azoospermia. In the current study, 100 infertile patients with azoospermia and 100 normal controls were analyzed for genetic alterations in the active site coding region of SEPT12, using PCRSequencing technique and mutational analysis. Genotype analysis indicated that G5508A polymorphic SEPT12 alleles were distributed in three peaks of frequency in diseases group (GG, GA and AA) and two peaks in control group (GG and GA). The frequencies of the G5508A allele and the genotype were significantly difference between the azoospermic patients and controls (p ≤ 0.05 by chi-square test). This finding suggests that G5508A variant in the SEPT12 gene may associate with the increased susceptibility to azoospermia.