ABSTRACT: In this study, we aim to explore the correlation between single nucleotide polymorphisms (SNPs) in the P2X7R gene and pulmonary tuberculosis (PTB) susceptibility in the Tibetan Chinese population in China. We examined 467 patients with active PTB and 504 healthy controls living in Xi'an and the surrounding area. Eight P2X7R SNPs were genotyped, and association analysis was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were tested by unconditional logistic regression analysis to evaluate the effects of the polymorphisms on PTB risk. P2X7R SNP association analyses were performed using SPSS 17.0 statistical packages and Microsoft Excel, SNP statistics software, Haploview software package (version 4.2), and SHEsis software platform. The results show that the "C" allele of rs656612 in the P2X7R gene was associated with an increased PTB risk by the additive model (OR = 1.307, 95% CI = 1.088-1.570, P = 0.004) and dominant model (rs656612, OR = 1.490, 95% CI = 1.153-1.926, P = 0.002). The "A" allele of rs208290 showed an increased PTB risk by the additive model (OR = 1.418, 95% CI = 1.179-1.706, P < 0.001) and dominant model (OR = 1.680, 95% CI = 1.297-2.177, P < 0.001), whereas the "A" allele of rs7958311 showed an increased risk by the additive model (rs7958311, OR = 1.260, 95% CI = 1.055-1.505, P = 0.011) and recessive model (OR = 1.609, 95% CI = 1.200-2.158, P = 0.001). After Bonferroni correction, rs208290 was found to be associated with PTB in the allele, dominant, and genotype models. In conclusion, our study revealed a significant association between three P2X7R gene polymorphisms (rs656612, rs208290, and rs7958311) and PTB in a Tibetan Chinese population.