Objective: This study aimed to investigate the clinical effect of vortioxetine on patients with depression. Methods: A total of 85 patients diagnosed with depression in our hospital from January 2018 to January 2019 were divided into control group (CG, n=42) and observation group (OG, n=43) using the random number table. The CG group was given duloxetine and the OG group was given vortioxetine. The interventions used in two groups were the same. After 2 months of continuous treatment, their brain-derived neurotrophic factor (BDNF) levels, social function, quality of sleep, depression improvement, and executive function were analyzed. Results: (1) BDNF levels in OG were higher than those in CG after 1 and 2 months of treatment (P<0.05). (2) After 2 months of treatment, OG had lower scores in terms of social life, work and family responsibilities than those in CG (P<0.05). (3) The improvement rate of OG was 83.72% and that of CG was 88.10% (P>0.05). (4) At the end of 2 months of treatment, and 1 month and 3 months after treatment, PSQI scores in OG were lower than those in CG (P<0.05). (5) At 3 months after treatment, the correct responses (CR) and categories completed (CC) in OG were better than those in CG (P<0.05) whilst random errors (RE) and perseverative errors (PE) were decreased as compared with CG (P<0.05). The response administered (RA) was not significantly different from CG (P>0.05). (6) The incidence of adverse reactions was 16.28% in OG and 35.71% in CG, respectively (P<0.05). Conclusion: Vortioxetine used in patients with depression could increase BDNF levels, improve depression and restore cognitive and executive function to normal. The higher recovery rate promises its application.