Abstract: Objective: To evaluate the efficacy and safety of Mirtazapine in treatment for resistant functional dyspepsia with depression. Methods: Seventy-five FD patients with depression were randomly assigned to receive mirtazapine、paroxetine or regular treatment for 6 weeks. The therapeutic efficacy was evaluated by dyspepsia symptom judgment and the Hamilton depression scale (HAMD). The safety was assessed by adverse effects. Results: ①At the end of 6th week , there is significant difference in the scores of dyspepsia syndrome among three groups . ②There is significant difference in the scores of HAMD between mirtazapine group and control group. But There is no significant difference in the scores of HAMD between mirtazapine group and paroxetine group.③The adverse effects associated with mirtazapine was dizzy（16%）、body weight increased （16%）、fatigue（8%）、lethargy（8%） .The adverse effects are mild and need no treatment. Conclusion: Mirtazapine can improve integrative symptoms of FD patients with the treatment of antidepression, it is effective and safe in treatment for resistant functional dyspepsia with depression.