〔Abstract〕 Objective To explore the effect of escitalopram combined with cognitive behavioral therapy in elderly patients with depression. Methods A total of 80 elderly patients with depression treated in Jiaozuo Fourth People's Hospital from January 2019 to January 2021 were selected and divided into random number table method, with 40 patients in each group. The control group received escitalopram treatment, and the observation group received cognitive behavioral therapy in addition to escitalopram treatment. The adverse mood, cognitive function and quality of life of patients in the two groups were compared before and after treatment. Results After treatment, the scores of Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) in the two groups were lower than before, the differences were statistically significant (P < 0.05). After treatment, HAMA and HAMD scores in the observation group were lower than those in the control group. The differences were statistically significant (P < 0.05). After treatment, the scores of Montreal Cognitive Assessment Scale (MOCA) and the comprehensive assessment scale of quality of life (GQOLI) in the two groups were higher than before treatment, and the differences were statistically significant (P < 0.05). After treatment, the scores of MOCA and GQOLI in the observation group were higher than those in the control group. The differences were statistically significant (P < 0.05). ConclusionEscitalopram combined with cognitive behavioral therapy can reduce depression degree and improve cognition and quality of life in elderly patients with depression.