The senile lung adenocarcinoma patients harboring an activating epidermal growth factor receptor (EGFR) mutation shows good and rapid response to EGFR tyrosine kinase inhibitors (TKIs). Whether gefitinib combined withγ-ray stereotactic body radiation therapy has better eficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen is stil under investigation.Methods: The 42 senile lung adenocarcinoma patients with EGFR mutations were divided into 2 groups according to the therapy method. Group A was the 22 patients treated with gefi-tinib combined with γ-ray stereotactic body radiation therapy (SBRT). Group B was the 20 patients treated with gefitinib alone. Al of the patients received gefitinib of 250 mg/d from the first day until disease progression or other reasons. The patients of Group A were treated with γ-ray stereotactic body radiation therapy from the second day. Radiation fields included the primary lesions and the integration of lymph nodes. Dose curve of this group was 50%-80%. Encircled dose was 4.0-6.5 Gy per frac-tion and the range of total dose was 40-52 Gy. We treated the patients 8-12 times and treated five times every week.Results:Al the patients were examined by enhanced double helix CT at the second month. The tumor response rate (RR) of group A was 81.8% (18/22). Disease control rate (DCR) was 90.9% (20/22). The median overal survival (OS) was 24.2 months (range 8-58 months ) and the progression-free survival (PFS) was 18.6 months. The overal 1-year survival rate was 72.3%(16/22) and 2-year survival rate was 54.5% (12/22). The main side efects included skin rash and diarrhea. The RR of group B was 50.0 % (10/20). DCR was 75.0% (15/20). OS was 17.4 months (range 6-32 months ) and PFS was 12.1 months. The overal 1-year survival rate was 60.0% (12/20) and 2-year survival rate was 40.0% (8/20). The main side efects included skin rash and diarrhea. The group A who were treated with gefitinib combined with γ-ray stereotactic body radiation therapy had a higher short term therapeutic efects (RR) and long term therapeutic efects (OS) than group B who were treated with gefitinib alone respectively (81.8% vs 50.0%,P = 0.029 < 0.05,χ2= 4.773 and 24.2 vs 17.4,P = 0.024 < 0.05,χ2 = 5.098).Conclu-sion:Gefitinib combined with γ-ray stereotactic body radiation therapy has better eficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen. The side afects are acceptable.