OBJECTIVE： To study the association of 5-HTR1A/2A receptor gene polymorphism with antidepressant efficacy of selective 5-serotonin reuptake inhibitors （SSRIs）， and to provide reference for rational use of SSRIs. METHODS： In perspective study， 85 depressive inpatients met inclusion criteria were selected from Inner Mongolia Autonomous Region People’s Hospital during Oct. 2016-Oct. 2017. They were randomly given one kind of SSRIs as paroxetine， sertraline or escitalopram oxalate， for 8 weeks. They were divided into valid group （HAMD reduction rate≥50％） and invalid group （HAMD reduction rate＜50％） according to HAMD reduction rate calculated by HAMD score after treatment. Difference of genotype distribution and genotype distribution frequency of 5-HTR1A （rs6295） and 5-HTR2A （rs6313， rs6311） were analyzed by χ2-test in 2 groups. t-test comparison significantly influenced the effects of genotype on HAMD reduction rate. RESULTS： There were 45 patients in valid group and 40 patients in invalid group； there was no statistical significance in the difference in nationality， gender or age between 2 groups （P＞0.05）. There was statistical significance in the distribution frequency of 5-HTR1A（rs6295） allele G and C between 2 groups （χ2＝13.75，P＜0.001）； there was no statistical significance in genotype distribution （χ2＝4.72，P＝0.09）. There was statistical significance in the distribution frequency of 5-HTR2A（rs6313） allele G and A with 5-HTR2A（rs6311） allele C and T （χ2＝15.20， 15.20， P＜0.001）. There was statistical significance in difference of genotype distribution （χ2＝23.68， 23.68， P＜0.001）. There was no statistical significance in HAMD reduction rate among 5-HTR2A（rs6313）G/A， G/G， A/A genotypes （P＞0.05）. There was no statistical significance in HAMD reduction rate between 5-HTR2A（rs6311）T/T genotype and C/C genotype， between 5-HTR2A（rs6311）T/T genotype and C/T genotype （P＞0.05）. HAMD reduction rate of C/C genotype was significantly higher than that of C/T genotype （P＝0.02）. CONCLUSIONS： 5-HTR2A （rs6313， rs6311） gene polymorphism may be associated with clinical efficacy of SSRIs for depression. 5-HTR2A（rs6311） C/C genotype is hopeful as a efficacy predictor of SSRIs in the treatment of depression.