Recent studies have suggested that susceptibility to chronic obstructive pulmonary disease (COPD) might be related to the length polymorphism of (GT)(n) repeat in the 5'-flanking region of heme oxygenase-1 (HOX-1) gene. However, there has been no research about the relationship between the polymorphism of HOX-1 gene and severity of COPD. The polymorphism of HOX-1 gene in 452 patients with COPD from Han population in Southwest China was analysed by fragment analysis. The frequencies of the HOX-1 genotype were compared with the stage of COPD of each patient. The HOX-1 genotypes were classified into two groups: group I were individuals with class L allele (the number of GT = 32 repeats), and group II were those without class L allele (the number of GT < 32 repeats). The genotypic frequency of the HOX-1 group I was significantly higher than group II in the very severe COPD patients (36.8% vs 22.4%, P < 0.01, OR = 2.0, 95% CI 1.3 - 3.1), while the genotypic frequency of the HOX-1 group II was lower in the mild COPD (16.0% vs 26.0%, P = 0.02, OR = 0.5, 95% CI 0.3 - 0.9). However, in moderate and severe stages COPD, there were similar genotypic frequencies between HOX-1 group I and group II. Genetic polymorphism in HOX-1 is associated with the severity of COPD in Southwest China. COPD patients with class L allele may be susceptible to develop very severe COPD. Conversely, the COPD patients without class L allele may be more easily stabilized on mild COPD.