A retrospective case-control study was carried out in the Han-Chinese population to determine the polymorphisms of xeroderma pigmentosum complementation group C (XPC) gene on the risk of idiopathic azoospermia or oligozoospermia. The Ala499Val (C>T) and Lys939Gln (A>C) polymorphism of XPC gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism in three groups of infertile men (172 patients of azoospermia, 25 patients of severe oligozoospermia, 55 patients of oligozoospermia) and 228 fertile men. Increased risk of idiopathic azoospermia, but not oligozoospermia was associated with the XPC variant genotypes of Ala499Val (C>T) [adjusted odds ratio (OR) = 1.67, 95% confidence interval (CI) = 1.04-2.68 for CT heterozygote and adjusted OR = 2.03, 95% CI = 1.10-3.75 for TT homozygote] compared with CC homozygous wide-type. The Lys939Gln (A>C) polymorphism was not related to spermatogenic failure. The combined risk alleles analysis and haplotype analysis showed that ORs increased as the number of the risk alleles increased and the 499T-939C haplotype had a significantly increased risk of idiopathic azoospermia (OR = 7.97; 95% CI = 3.51-18.07) compared with other haplotypes. The results suggest that XPC Ala499Val (C>T) polymorphism is correlated with high risk of idiopathic azoospermia in the Han-Chinese population.