Objective To study clinical efficacy and toxicity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib combined with whole brain radiotherapy in the non-small cell lung cancer (NSCLC) with brain metastases and to evaluate its effectiveness and safety.Methods In accordance with the random digital number method, Sixty-three NSCLC patients with brain metastases were divided into erlotinib combined with whole brain radiation therapy group (33 cases) and whole brain radiotherapy alone group (30 cases), each patient received the whole brain radiotherapy, DT (3 000-3 600)cGy/(10-12) F.Erlotinib combined with whole brain radiotherapy group received oral erlotinib, at a dose of 150 mg per day from the beginning of the whole brain radiotherapy, at least two months until after the completion of radiation therapy.All patients were evaluated in the efficacy of radiotherapy at the end of two months.Results The metastases objective response rate and disease control rate of erlotinib combined with whole brain radiation therapy group and whole brain radiotherapy alone group were respectively 54.6％, 13.3％ (x2 =11.744, P =0.001) and 91.0％ , 60.0％ (x2 =8.276, P =0.004).The objective response rate and disease control rate in the two groups were respectively 39.3％, 10.0％ (x2 =7.166, P =0.007) and 84.8％, 40.0％ (x2 =7.759, P =0.005).Stratified analysis showed that in erlotinib combined with whole brain radiotherapy group, the objective response rate and disease control rate of EGFR mutation positive and negative subgroup were respectively 76.5％, 33.3％ (x2 =6.248, P=0.012) and 100％, 77.7％ (x2 =4.093, P=0.043).The 1-year sur vival and progression-free survival rates of the two groups were 57.6％, 30.0％ and 42.4％, 16.7％, the differences were statistically significant (x2 =4.840, P =0.028;x2 =4.950, P =0.026).The main adverse events of erlotinib combined with whole brain radiotherapy group were mild to moderate rash, diarrhea, and no treatment-related deaths occurred.Conclusion Erlotinib combined with whole brain radiotherapy for the NSCLC patients with brain metastases has some effect, and the adverse reactions are mild, which can be used as a treatment option for NSCLC brain metastases.