TP53 is a tumor-suppressor gene which is involved in multiple pathways including apoptosis, transcriptional regulation, and cell cycle control. To analyze whether the TP53 gene Arg72Pro polymorphism (rs1042522) is responsible for susceptibility to idiopathic infertility in southeast Chinese Han males, we used the PCR restriction fragment length polymorphism technique to detect the genotype distribution of 361 infertile men (including 212 with non-obstructive azoospermia and 149 with severe oligozoospermia) in comparison with 384 fertile controls. Genotyping was confirmed by DNA sequencing from randomly selected samples. The frequency of rs1042522 indicated an association with risk of idiopathic male infertility under a dominant mode (GG + GC genotypes vs. CC genotype, P = 0.013; χ(2) = 6.169; OR = 1.581; 95%CI = 1.1-2.272; df = 1). Comparison of the allele frequencies revealed a significantly higher incidence of Arg allele among azoospermia group compared with controls (P = 0.001; χ(2) =10.864; OR = 1.502; 95%CI = 1.177-1.917; df = 1). Our data suggest that the Arg allele was related only to azoospermia, not to severe oligozoospermia (P = 0.133; χ(2) = 2.261; OR = 1.23; 95%CI = 0.939-1.611; df = 1). This study indicated that the TP53 gene Arg72Pro polymorphism of the spermatogenic pathway may be associated with idiopathic infertility in southeast Chinese Han males.