Abstract: Objective To investigate the efficacy and side effects of erlotinib plus whole brain radiotherapy（WBRT） in the treatment of lung cancer with brain metastases. Methods Forty-two cases of lung cancer with brain metastases patients from January 2011 to June 2012 in our hospital were randomly divided into treatment group（n=22）and control group（n=20）. 22 patients in treatment group were treated with erlotinib 150mg orally， once per day， combined with WBRT with total dose of 30-36Gy， 3Gy per fraction， five times per week. If the number of brain metastatic lesions were 1-2， shrinkage wild of brain metastases should need extral 16-20Gy／8-10 times after WBRT. Twenty patients in control group were received chemotherapy for 2 cycles（21days was a cycle），and then treated with WBRT， with the same dose and method to treatment group. Patients with ECOG scored 0-1 points were treated by AP or DP solutions. Patients with ECOG scored 2 points were treated with pemetrexed chemotherapy. The curative effects， the survival rate and adverse reaction of two groups were observed and evaluated. Results A total of 42 patients could be evaluated. The RR of brain metastases in treatment group and control group was 86.4％ and 70.0％， respectively（P＞0.05）. The RR of lung primary tumor in treatment group and control group was 40.9％ and 35.0％， respectively（P＞0.05）. The median progress free survival was 8.5 months in treatment group and 4.5 months in the control group（P＞005）. The median survival time was 14.0 months in the treatment group and 9.8 months in the control group（P＞0.05）. 1-year survival rate of two groups were 59.1％ and 450％， and 2-year survival rates were 27.3％ and 15.0％， respectively. They were no statistically significant difference（P＞0.05）. The main adverse reactions in treatment group were only rash and diarrhea， mostly gradeⅠ-Ⅱ， which could be tolerated. The obvious bone marrow suppression and gastrointestinal side effects had no occurrence. In the control group， the adverse reactions were mainly bone marrow suppression， gastrointestinal side effects such as nausea vomiting， which could be relieved by symptomatic treatment. Conclusion Erlotinib combined with WBRT in the treatment of lung cancer with brain metastases can prolong the survival time and were well tolerated for patients.