【Abstract】 Objective To study the efficacy of risperidone combined with ziprasidone in the treatment of post-schizophrenia patients with depression and its impact on cognitive function and quality of life. Methods 116 patients with postschizophrenia depression treated in our hospitalfrom March 1, 2017 to March 31, 2018 were enrolled in this study and divided into control group (58 cases) and study group (58 cases) , according to the principle of random number table. The control group was treated with risperidone tablets alone, and the study group was treated with risperidone in combination with ziprasidone. The changes of mental state, depression state, cognitive function and quality of life before and after treatment were compared between the two groups. Results The total effective rate of treatment in the study group (94. 8%) was higher than that in the control group (75. 9%) (P<0.05). After treatment, the PANSS and CDSS-C scores of the two groups were significantly lower, and the study group was lower than the control group(P<0.05). After treatment, the cognitive function LOTCA scores of the two groups were higher, and the study group was higher than the control group (P<0.05). After treatment, the quality of life scores of the two groups were significantly increased, and the study group was higher than the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the study group and the control group (P〉0.05). Conclusion Risperidone combined with ziprasidone is effective in the treatment of post-schizophrenia depression. It can effectively improve the mental state and depression of patients, promote the recovery of cognitive function and improve the quality of life of patients.