Whole brain radiotherapy (WBRT) has been the mainstay treatment of brain metastases (BM) in non-small cell lung cancer (NSCLC) patients for years. Temozolomide (TMZ) could penetrate the blood-brain barrier and some studies showed that TMZ plus MBRT may improve clinical effectiveness. This meta-analysis is aim to evaluate the clinical effectiveness and safety of TMZ plus MBRT in the NSCLC patients with BM.We systematically searched databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and four Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database) without language restrictions from inception until July 26, 2019. Randomized controlled trials (RCTs) which compared TMZ plus WBRT with single WBRT in the advanced NSCLC patients with BM were included. The outcomes analysis reported objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), quality of life (QOL), and adverse effects. Two reviewers will independently extract data from the selected studies and assess the quality of studies. Statistical analyses will be performed using Review manager 5.3 software. Random-effects or fixed models were used to estimate pooled hazard ratio and relative risk.This systemic review and meta-analysis will evaluate the effects of TMZ plus MBRT in the NSCLC patients with BM in RCTs.Our study will provide evidence to judge if TMZ plus MBRT are effective treatment for NSCLC patients with BM.