Background: To observe the efficacy of temozolomide in combination with radiotherapy against metastatic brain tumors. Materials and Methods: This study was a prospective, observational, open-label study, conducted in clinical practice implanted for metastatic brain tumor patients. A total of 106 patients with metastatic brain tumors were enrolled in this study, and according to the sequence of admission, they were randomized into the experiment group (temozolomide + radiotherapy) and the control group (radiotherapy). During the 24 months of follow-up, we compared the clinical efficacy, recurrence time, survival time and quality, and the adverse reactions of the patients between two groups. Results: Short-term remission after treatment was higher in the experimental group compared to control (P<0.05). During the 24-month follow-up, we found that patients in the experiment group had longer recurrence time and survival time than their counterparts in the control group (P < 0.05). After treatment, the scores of the life quality of patients in the experiment group were better than those in the control group (P<0.05). Also, there was a lower rate of the incidence of the adverse reactions in the experiment group (P<0.05). Conclusion: For metastatic brain tumors, temozolomide in combination with radiotherapy works better as a safe and reliable strategy in prolonging the survival time, increasing life quality while reducing the adverse reactions. The strength of this study was evaluating the quality of life as an important outcome of the chemotherapy+radiotherapy regimen.