The aim of this study was to determine the frequencies of single-nucleotide polymorphisms (SNPs) in the Smad3 gene in the Chinese population and their possible association with chronic obstructive pulmonary disease (COPD). The frequency distribution of nine SNPs in the introns of the Smad3 gene was determined in both the COPD patients and control groups by the TaqMan polymerase chain reaction method using a minor groove binder probe. The genotype distribution of the rs28683050 polymorphism in control subjects was as follows: CC, 67.6%; CT, 27.0% and TT, 5.4%; and in COPD patients was as follows: CC, 47.0%; CT, 38.8% and TT, 14.2%. Therefore, a significant difference in allelic and genotypic frequencies between the COPD patients and control subjects is observed. Their genotypic distribution was not significantly different from that predicted by Hardy–Weinberg's equilibrium. The frequency of the TT genotype in the COPD patients was significantly higher than that in controls (14.2% versus 5.4%, odds ratio [OR] = 3.762, 95% confidence interval: 1.650–8.581, P = 0.002), and the frequency of the T allele in the COPD patients was significantly higher than that in controls (81.1% versus 66.4%, OR = 1.774, 95% confidence interval: 1.354–2.324, P = 0.001). These data show that the rs28683050 polymorphism of the Smad3 gene may be associated with COPD.