Acne is a multifactorial, chronic inflammatory disease of pilosebaceous unit in which cytokines have been implicated in the pathogenesis. Although it is thought to be an inherited disease, there are limited data supporting the relevant genetic elements. Tumor necrosis factor-alpha (TNF-alpha) is one of the proinflammatory cytokines involved in the acne pathogenesis. Several single-nucleotide polymorphisms (SNPs) have been identified in the human TNF-alpha gene promoter. The polymorphism at position -308, which involves substituting guanine (G) for adenine (A) (TNFA-308 G/A) has been linked to increased susceptibility to several chronic inflammatory diseases. The aim of this study was to determine the TNFA-308 G/A polymorphism in acne and to examine whether there is a relationship between this polymorphism and disease susceptibility. Exactly, 113 patients with acne and 114 healthy control subjects were included in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used for analysis of the TNFA-308 G/A polymorphism. We found that the frequency of the TNFA-308 GA genotype was statistically significantly increased in patients compared with healthy controls (P < 0.001). There was no association between TNFA genotypes and severity of acne (P > 0.05). There was also no significant difference between male and female patients. Our results suggest that TNFA-308 G/A polymorphism may contribute to a predisposition to acne in Turkish population.