Objective To investigate the association of 5-HT2A receptor (5-HTR2A) gene -1438G/A polymorphisms with obsessive-compulsive disorder (OCD) and efficacy of sertraline treatment. Methods One hundred and twenty-seven patients with OCD were selected, and were treated with sertraline for 8 weeks, with 200 mg/d as the highest dose of sertraline. The efficacy was rated by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Polymerase chain reaction-restriction fragment length polymorphism was used to detect -1438G/A polymorphisms of 5-HTR2A gene in patients with OCD and healthy controls (n=224). Results There were significant differences in the allele distribution frequencies between OCD group and control group (P<0.05), while there was no significant difference in the genotype distribution frequency between two groups (P>0.05). There was no significant difference in the allele distribution frequency between sertraline effective group and sertraline invalid group (P>0.05), while there were significant differences in the genotype distribution frequencies between two groups (P<0.05). There were significant differences in the allele distribution frequencies and genotype distribution frequencies between females in OCD group and those in control group (P<0.05), between OCD early onset group and control group (P<0.05), between OCD early onset group and OCD late onset group (P<0.05), and between patients only with obsessive-compulsive behavior in OCD group and control group (P<0.05). Conclusion 5-HTR2A gene -1438A allele may be the risk factor of development of OCD. -1438G/A polymorphism may be associated with female gender, early disease onset and obsessive-compulsive behavior as the only symptom in OCD. The genotype of 5-HTR2A gene -1438G/A polymorphisms may be associated with the efficacy of sertraline treatment in OCD.