Objective: Chronic obstructive pulmonary disease (COPD) is a complex disease in which multiple genes and their interaction with environmental factors contribute to disease development. Recent genome-wide association studies in COPD revealed several gene variants. However, there have no studies were performed in Chinese Li population, and additional studies in multiple ethnic groups are needed. We investigated genetic associations in Li population COPD and control subjects. Methods: We genotyped 25 single nucleotide polymorphisms located in 13 genes in a case-control study with 234 COPD cases and 240 controls at Hainan Province Hospital. Odds ratios and 95% confidence intervals were estimated using the chi-squared (chi(2)) test, genetic model analysis, haplotype analysis, and stratification analysis. Results: We identified that the minor alleles of rs667282 and rs2823743 were associated with a 1.35-fold increased risk of COPD and the minor alleles of rs8048576 was associated with a 0.68-fold decreased risk of COPD. In the genetic model analysis, we found rs667282 and rs2823743 were associated with increased COPD risk and rs13080 was associated with decreased COPD risk. Further stratification analysis showed that rs6265 displayed a significantly increased lung cancer risk (OR=1.87) in the non-smokers. Conclusion: Our results verified that multigenetic variants of contribute to COPD susceptibility in the Chinese Li population. Additionally, we found that smoking may interact with polymorphisms to contribute to COPD susceptibility. And this is the first time that smoking and multigenetic index on the risk of COPD in the Chinese Li population has been reported.