This study investigated the correlation between surfactant protein-A (SP-A) polymorphism and the susceptibility of chronic obstructive pulmonary disease (COPD) in Xinjiang Uighurs. Genomic DNA was extracted from peripheral blood of 194 COPD smokers and 201 healthy smokers of Uighur who were hospitalized in or paid a visit to one of the four Xinjiang-based hospitals involved in the study, from March 2009 to December 2010. Single nucleotide polymorphisms (SNPs) were studied at aa62 (CCA/CCG rs1136451) and aa219 (CGG/TGG, rs4253527) in SP-A. Genotypes were determined by using the TaqMan polymerase chain reaction (PCR). Our results showed that genotype frequencies were different between the COPD and normal smokers in aa62 (x (2)=6.852, P=0.033). There were also significant differences in allele genotype frequencies between the COPD and the control and allele G might decrease the risk COPD (x (2)=6.545, P=0.011; OR=0.663; 95% CI: 0.484-0.909). The result suggested that polymorphism of aa62 (CCA/CCG, rs1136451) of SP-A may be associated with the susceptibility to COPD in Xinjiang Uighurs.