Hematopoietic cell kinase (Hck), a Src family kinase, has been recently suggested to be implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). The present study aims to analyze the association of polymorphism of Hck gene with COPD in a Chinese population. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-sequence-specific primer method (PCR-SSP) were used to type Hck polymorphisms in 120 patients with COPD and 100 healthy controls. There were significant differences in the genotype and allele distribution of -627 G/T polymorphism in Hck gene between cases and controls (P<.05). The GT genotype was associated with a significantly increased risk of COPD as compared with the GG genotype (Odds ratio [OR]=2.60, 95% confidence interval [CI]: 1.39-4.48; P=.002). Moreover, individuals carrying T allele had a significantly higher risk for developing COPD than those carrying G allele (OR=2.19, 95% CI: 1.26-3.79; P=.005). In haplotype analysis, compared with CG(deletion) haplotype, CT(insertion) haplotype was associated with a significantly increased risk of COPD (OR=2.66, 95% CI: 1.22-5.78; P=.011). These findings suggest the Hck gene polymorphisms may contribute to COPD susceptibility in Chinese population.