OBJECTIVE：To observe the clinical efficacy and safety of olanzapine combined with quetiapine fumarate in the treatment of schizophrenia. METHODS： 116 patients with schizophrenia were randomly divided into observation group and control group. Control group was orally given 5 mg Olanzapine tablet by twice， then the dose was gradually increased based on severity degree after 5-7 d， each additional 5， and increased to 5-20 mg within 2 weeks， and then maintained treatment dose until 8 weeks. Observation group was additionally given 200 mg Quetiapine fumarate tablet by twice， then the dose was gradually increased based on severity degree after 5-7 d， each additional 100 mg， and increased to 800-1 200 mg within 2 weeks， and then maintained treatment dose until 8 weeks. Clinical efficacy， the cognitive function index score， positive and negative syndrome scale （PANSS） score， side effects scale （TESS） score， incidences of extrapyramidal reactions （EPS） and adverse reactions in 2 groups were observed. RESULTS： The total effective rate in observation group was significantly higher than control group， incidence of EPS was significantly lower than control group， TESS scores in observation group were significantly lower than control group after 4 weeks and 8 weeks， incidence of adverse reactions was significantly lower than control group， the differences were statistically significant （P＜0.05）. Before treatment， there were no significant differences in the cognitive function index score and PANSS score between 2 groups（P＞0.05）； after treatment， the cognitive function index scores in 2 groups were significantly higher than before， observation group was higher than control group， and it gradually increased by the extension of treatment， PANSS scores were significantly lower than before， observation group was lower than control group， and it gradually decreased by the extension of treatment， the differences were statistically significant （P<0.05）. CONCLUSIONS： Olanzapine combined with quetiapine fumarate has better efficacy than olanzapine alone in the treatment of schizophrenia， and it can significantly improve the cognitive function index scores of patients， with good safety.