Objective:To explore the association between α5 subunit of gamma-aminobutyric acid receptor subtype 5(GABRA5) gene polymorphism and executive function in patients with major depressive disorder.Methods:From August 2018 to September 2020, one hundred and eighty depressed patients diagnosed by DSM-Ⅳ-TR criteria were included from Xuzhou Eastern Hospital, meanwhile 120 healthy controls with matching demographic characteristic were recruited.Gene polymorphisms were detected through the elbow vein blood of all subjects. The severity of the patients was assessed by 17 items Hamilton depression scale(HAMD-17). The executive function of subjects was tested by Wisconsin card sorting test (WCST) and event-related potential P300.The t test and χ2 test were used for statistic analysis by SPSS 17.0. Results:The cognitive function of depression patients with GABRA5 receptor gene carrying T allele was significantly lower than that of patients with C allele ( t=2.35-3.45, P<0.05). The cognitive dysfunction was associated with sleep and anxiety/somatization symptoms in depression patients ( r=-0.197-0.409, P<0.05). Anxiety/somatization symptoms in patients with depression partially mediated the association between GABRA5 receptor gene polymorphism and cognitive dysfunction(effect value=-0.611, 95% CI=-1.393--0.057). Conclusion:The GABRA5 receptor gene polymorphism is associated with cognitive dysfunction in patients with depression, and anxiety/somatization symptoms partially mediate the impairment of cognitive function caused by GABRA5 receptor gene polymorphism.