Background and Objective: Tuberculosis (TB) caused by Mycobacterium tuberculosis, is an infectious disease in human which kills nearly three millions of people annually. Approximately, one - third of the world populations are infected with this bacteria and 5 - 10 % of them develop the active form of the disease. Individuals are different in susceptibility to TB infection. These differences might be due to the host characteristics especially genetic factors. TNF-α as a pro-inflammatory cytokine, play a key role in host defense against tuberculosis. Presence of mutation in this gene can influence the effectiveness, performance and capability of immune responses against TB infection. The Aim of this study was to investigate the frequency of TNF-α gene polymorphisms and its relation with susceptibility to the pulmonary TB. Materials and Methods: Sixty healthy controls and 60 TB patients were enrolled. Genotype of TNF-238, TNF -244, TNF-308, TNF -857 and TNF-863 were determined using PCR-RFLP method. The results were analyzed by Fisher Exact and χ 2 tests using SPSS v.14 and evaluated with Hardy–Weinberg equilibrium. Results: The results of this study showed a significant difference in TNF-308 and TNF -857 regions between the control and study groups (P < 0.05). Conclusion: Presence of mutation in TNF-308 and TNF -857 regions may increase the host susceptibility to mycobacterium tuberculosis and genotyping of these regions can be used for screening of the high risk individuals.