Conclusions: The -1438G/A polymorphism of 5-HT2A receptor gene may associate with obstructive sleep apnea hypopnea syndrome (OSAHS) in a Chinese Han population. Different genotypes of -1438G/A polymorphism may influence the ventilatory activity in response to hypoxia, and in turn the sleep breath status. Objective: This study was designed to assess the association of polymorphisms in all exons and promoter region of the 5-HT2A receptor gene with OSAHS in a Chinese Han population. Methods: A total of 315 subjects (210 patients and 105 controls) were included for genetic analyses of polymorphisms in all exons and promoter region of the 5-HT2A receptor gene. Results: Six single nucleoside polymorphism (SNP) sites were identified in the sequencing of the promoter and exons of the 5-HT2A receptor gene; however, genotypes and allele frequencies of the SNPs did not show significant differences between the patients and controls except the -1438G/A polymorphism. For SNP of -1438G/A, the A/A genotype was over-represented and the allele A was more frequent in the patients, while the G/A genotype was over-represented and the allele G was more frequent in the controls (p < 0.001, p = 0.005, respectively). In the patients, the A/A and G/A genotypes were over-represented in the subgroups with lowest nocturnal SaO(2) (LSaO(2)) <= 75% and LSaO(2) > 75%, respectively (p = 0.006).