Sox8, encoding a SRY-related HMG box transcription factor, is essential in Sertoli cells for germ cell differentiation via regulation of integrity of the blood-testis barrier (BTB) as well as Sertoli-germ cell adhesion. Inactivation of Sox8 gene in mice causes postnatal progressive spermatogenic failure, resulting in male infertility. This study aims to investigate whether variants of SOX8 contribute to pathogenesis of idiopathic non-obstructive azoospermia (NOA) or oligozoospermia. A case-control genetic study was conducted in which all exons and exon-intron boundaries of SOX8 gene were screened in 190 NOA and 139 oligozoospermia cases by Sanger sequencing. The detected variants were examined in 284 normospermic controls. Nine known single-nucleotide polymorphisms (SNPs) of SOX8 gene were identified, and four of them exist simultaneously in oligo/azoospermia patients. A comparison of allele/genotype frequencies of these variants showed no significant difference between oligo/azoospermia cases and controls. The results indicate that deleterious variants in SOX8 gene may not be a common cause for oligo/azoospermia in Chinese men. Considering ethnic diversity, SOX8 could not be ruled out as a candidate gene for male infertility. The role of SOX8-mediated Sertoli cell function and BTB integrity played in the pathogenesis of male infertility needs to be further explored in other populations.