〔Abstract〕Objective To analyze the clinical effects of using antidepressants in the treatment of patients with malignant tumor pain. Methods From January 2015 to March 2020, 48 cases of malignant tumor patients admitted to the Hospice Unit of the Affiliated Hospital of Guangdong Medical University were selected as the research objects, and they were divided into two groups using a random method, the control group and the observation group, with 24 cases in each group. Among them, the control group used conventional chemotherapy for treatment, and the observation group used antidepressant drugs for intervention on the basis of conventional chemotherapy. The treatment effects of patients were compared. Results Before treatment, the difference in VAS scores between the two groups of patients was not statistically significant (P > 0.05); after treatment, the VAS scores of the patients were reduced, and the VAS seores of the observation group was lower than that of the control group, the difference was statistically significant (P < 0.05). Before treatment, the difference in SDS scores between the two groups of patients was not statistically significant (P > 0.05); after treatment, the SDS scores of the patients were reduced, and the SDS scorces of the observation group was lower than that of the control group, the difference was statistically significant (P < 0.05) . The quality of life scores of patients in the observation group were higher than those in the control group, and the differences were statistically significant (P < 0.05). Conclusion In the process of treatment of patients with malignant tumor pain, reasonable use of antidepressants is beneficial to the relief of pain and depression, and has positive value for improving the quality of life of patients.