The objective of this study was to assess the clinical efficacy and safety of concomitant or adjuvant tomozolomide with whole-brain irradiation (WBI) in patients with brain metastases. MEDLINE, EMBASE, Cochrane Library, Chinese Biomedical Literature Database were searched to identify relevant original published trails, and the references of eligible studies were manually screened. Randomized controlled trails reported in any language, comparing concomitant or adjuvant temozolomide (TMZ) and WBI with WBI alone in patients with brain metastases, were eligible for inclusion. Two investigators independently assessed the quality of included trials and extracted data. The RevMan 5 software was used for statistical analysis. Four trials involving 280 patients were included. The result showed that the group TMZ+WBI was superior to group WBI in partial response, stable disease, progressive disease, and objective response with the pooled risk ratio value and 95% confidence interval, respectively, 1.89 (1.19-3.02), 0.82 (0.45-1.50), 0.29 (0.10-0.78), and 1.72 (1.32-2.24). The incidence of gastrointestinal symptoms and > or =grade 3 myelosuppression presented statistical difference, TMZ+WBI group is higher than WBI group, the pooled risk ratio value and 95% confidence interval were 3.75 (1.04-13.44) and 13 (1.75-96.79), respectively. The currently available evidence showed that the combination of TMZ and WBI may moderately improve the response rate, but accordingly increase the incidence of gastrointestinal symptoms and myelosuppression. Future large-scale, high-quality, placebo-controlled, double-blind trials are needed.