Objective To investigate the clinical effect of fractionated stereotactic radiotherapy combined with temozolomide chemotherapy in the treatment of brain metastases. Methods A total of 50 patients with brain metastases with histopathological evidence and intracranial metastases diagnosed by enhanced MRI were selected from Yichun People′s Hospital from February 2018 to December 2019. According to the random number table method, they were divided into the control group and the study group, with 50 cases in each group. The control group was treated with fractionated stereotactic radiotherapy, the study group was treated with fractionated stereotactic radiotherapy and temozolomide chemotherapy. The total effective rate, total incidence of adverse reactions, Karnofsky score before and after treatment,1-year survival rate and recurrence rate after treatment were compared between the two groups. Results The total effective rate of the study group was higher than that of the control group, the difference was statistically significant (P＜0.05). The total incidence of adverse reactions in study group was lower than that in control group, and the difference was statistically significant (P＜0.05). After treatment, the Karnofsky score of the study group was higher than that of the control group, and the difference was statistically significant (P＜0.05). The recurrence rate of half a year and one year in the study group were lower than those in the control group, and the one-year survival rate was higher than that in the control group, and the differences were statistically significant (P＜0.05). Conclusion Fractional stereotactic radiotherapy combined with temozolomide chemotherapy can improve patients′ Karnofsky score, prolong the survival rate,and reduce the recurrence rate of patients with brain metastases.