Abstract: Objective To explore the genetic polymorphisms of interleukin-17 (IL-17), toll-like receptors 4 (TLR4) and purnergic receptor P2X7 (P2X7) in association with the chronic obstructive pulmonary disease (COPD). Methods A case-control study was performed by recruiting 152 COPD cases from the Third People's Hospital of Nantong from June 2015 to May 2016. Healthy controls were selected from a group of people attending the physical examination and were frequency-matched to the cases by sex and age. Genotyping was performed by using the TaqMan allelic discrimination technology. The association was estimated by using odds ratio (OR) and 95% confidence interval (CI). Results After the Bonferroni correction, the polymorphisms of rs2275913 and rs763780 in IL-17 gene, rs10759932 and rs2737190 in TLR4 gene, and rs1718119 in P2X7 gene were significantly associated with the altered risks of COPD (all P<0.05). Individuals carrying rs2275913 allele A had a reduced risk of COPD, with the OR of 0.62(95% CI:0.46-0.86). Individuals carrying rs763780 allele C had an increased risk, with the OR of 1.96(95% CI:1.29-2.98). Individuals carrying rs10759932 allele C had a reduced risk, with the OR of 0.49(95% CI:0.34-0.73). Individuals carrying rs2737190 allele G had a reduced risk, with the OR of 0.51(95% CI:0.37-0.71). Conclusions Genetic polymorphisms of IL-17, TLR4 and P2X7 were significantly associated with the altered risks of COPD.