Background Inherited factors are involved in the development of chronic obstructive pulmonary disease (COPD). This study was designed to investigate the relationship between polymorphisms of HDEFB1 668 C/G and 1654G/A loci and susceptibility to COPD in Chinese Han population.Methods After the process of extracting genomic DNA from peripheral blood of COPD smokers and healthy smokers, the loci of genotypes 668C/G and 1654G/A were determined by polymerase chain reaction-restriction fragment length polymorphism analysis and polymerase chain reaction-single strand conformation polymorphism analysis. Results With respect to HDEFB1 668 locus, the occurences of CC, CG, GG genotypes were 72.7%, 25.0%, 2.3% in COPD smokers and 53.2%, 38.3%, 8.5% in healthy smokers (P<0.05, respectively). The allele frequencies of 668 C and 668G were 85.2% and 14.8% in COPD smokers and 72.3% and 27.7% in healthy smokers (P<0.01, respectively, odds ratio was 2.32 with 95% confidence interval 1.37 to 3.72). As to HDEFB1 1654G/A locus, neither genotype distribution difference nor allele distribution difference was found when comparing COPD smokers with healthy smokers. Conclusion The polymorphism of HDEFB1 668C/G is associated with susceptibility to COPD in Chinese Han population; furthermore, the 668G allele represents relatively lower susceptibility to COPD. Background Inherited factors are involved in the development of chronic obstructive pulmonary disease (COPD). This study was designed to investigate the relationship between polymorphisms of HDEFB1 668 C / G and 1654G / A loci and susceptibility to COPD in Chinese Han population. Methods After the process of extracting genomic DNA from peripheral blood of COPD smokers and healthy smokers, the loci of genotypes 668C / G and 1654G / A were determined by polymerase chain reaction-restriction fragment length polymorphism analysis and polymerase chain reaction-single strand conformation polymorphism analysis. With respect to HDEFB1 668 locus, the occurences of CC, CG, GG genotypes were 72.7%, 25.0%, 2.3% in COPD smokers and 53.2%, 38.3%, 8.5% in healthy smokers (P <0.05, respectively) frequencies of 668 C and 668G were 85.2% and 14.8% in COPD smokers and 72.3% and 27.7% in healthy smokers (P <0.01, respectively, odds ratio was 2.32 with 95% confidence interval 1.37 to 3.72). As to HDEFB1 1654G / A locus, neither genotype distribution difference nor allele distribution difference was found when comparing COPD smokers with healthy smokers. Conclusion The polymorphism of HDEFB1 668C / G is associated with susceptibility to COPD in Chinese Han population; furthermore, the 668G allele means relatively lower susceptibility to COPD