Objective: TNF-α is one of the most important factors recognized in the pathogenesis of open-angle glaucoma. Therefore, the association of single nucleotide polymorphisms in the TNFRI gene and the promoter region of the TNFA gene with glaucoma susceptibility was investigated in the present study. Method: In total, 223 patients with glaucoma and 202 unrelated controls were genotyped by allele-specific oligonucleotide PCR and PCR- restriction fragment length polymorphism to determine TNFA –308 G/A and TNFRI +36 A/G polymorphisms, respectively. Results: In contrast to TNFRI polymorphisms, the genotypes of TNFA –308 G/A polymorphisms showed a significant difference between patients and controls (p = 0.0025). Of interest, the distribution of TNFA genotypes was significantly different between patients with primary open-angle glaucoma (p = 0.001) or pseudoexfoliative glaucoma (p = 0.001) and controls, while no difference was found when chronic angle-closure glaucoma patients were compared to controls (p = 0.72). Conclusion: In line with studies showing the role of TNF-α in open-angle glaucoma, the results of the present study showed that inheritance of the high producer TNFA –308 A allele might be a susceptibility factor for the development of open-angle glaucoma.