Objective To assess the efficacy and safety of a combination of Olanzapine and strong opioid drugs in treating cancer pain. Methods Clinical data of patients with cancer pain treated with strong opioids from January 2018 to August 2020 in Department of Oncology, Changzheng Hospital, Naval Military Medical University were retrospectively analyzed. Patients were divided into 4 groups according to the dose of olanzapine they received: group 10 mg/d, group 5 mg/d, group 2.5 mg/d and the control group. The change in NRS score of cancer pain after 1⁃week treatment was assessed. Adverse events (AEs) monitoring occurred throughout.Results Among the 6 patients who received Olanzapine 10 mg/d, 4 patients experienced 3⁃grade drowsiness, 2 patients experienced 3⁃grade fatigue, 1 patient experienced 3⁃grade constipation. This group was discontinued owing to the AEs. After 1⁃week treatment, the NRS score of the 3 groups were 3.9±1.5、3.5±1.4、4.8±1.0 for group 5 mg/d olanzapine 2.5 mg/d olanzapine and control group respectively. In the study, treatment with 5 mg/d olanzapine, compared with Control group, resulted in statistically significant improvement（P＝0.032）. Treatment with 2.5 mg/d olanzapine, compared with Control group, also resulted in statistically significant improvement（P＝0.002）. Treatment with 5 mg/d olanzapine, compared with Treatment with 2.5 mg/d olanzapine, didn′t result in any statistically significant improvement（P＝0.364）. Conclusion Treatment with a combination of 10 mg/d and 5 mg/d olanzapine with strong opioid drugs can significantly reduce the NRS score, improve the efficacy of cancer pain.