[Abstract] Objective: To observe the clinical effect of mosapride combined with ziprasidone in the treatment of functional dyspepsia patients with clinical depression . Methods: A total of 90 patients were enrolled from our hospital during July 2014 to July 2015. They were randomly divided into control group (45cases) with mosapride and ziprasidone treatment or observation group (45 cases) with only mosapride treatment. After 5-week treatment, the symptoms were observed and compared. Results: there was no significant difference in HAMD scores and symptom scores between the two groups before treatment. After treatment, the HAMD score in the observation group was significantly lower than that in the control group (0.2 V.S. 0.5). The total efficacy rate of the observation group was 88.89%, which higher than that of the control group, the total effective rate was 77.78%, P < 0.05. Conclusion : the administration of Mosapride combined with ziprasidone in the treatment of functional dyspepsia patients with depression showed good clinical effect, few side effects and high safety, it should be highly recommended in the clinical settings.