Objective To investigate the effect of Escitalopram combined with Mirtazapine on neurological function and levels of 5-hydroxytryptamine (5-HT) and mammalian target of Rapamycin (mTOR) in patients with post-stroke depression.Methods A total of 62 patients with post-stroke depression admitted to Shangrao Municipal Hospital from July 2019 to December 2020 were selected as the study subjects, and divided into control group (31 cases) and experimental group (31 cases) by random number table method.The control group was treated with Mirtazapine Tablets, and the experimental group was treated with Escitalopram Oxalate Tablets on the basis of the control group.Both groups were treated for 42 consecutive days.The ability of daily living scale (ADL), Pittsburgh sleep quality index (PSQI),Hamilton depression scale (HAMD), National Institutes of Health stroke scale (NIHSS) scores and serum 5-HT, mTOR levels were compared between the two groups before and after treatment.Results Before treatment, there were no significant differences in PSQI, ADL, NIHSS, HAMD scores, serum mTOR and 5-HT levels between the two groups (P>0.05).After treatment, PSQI, NIHSS and HAMD scores in the two groups were lower than those before, and PSQI,NIHSS and HAMD scores in experimental group were lower than those in the control group, with statistically significant differences (P<0.05).The ADL score, serum mTOR and 5-HT levels in the two groups after treatment were higher than those before, and the ADL score, serum mTOR and 5-HT levels in experimental group were higher than those in the control group after treatment, the differences were statistically significant (P<0.05).Conclusion Escitalopram combined with Mirtazapine can improve the daily life ability, sleep quality, depression, nerve function, serum 5-HT, mTOR levels, and improve clinical symptoms, which is worthy of clinical application.