Non-small cell lung cancer (NSCLC) has become the most common cancer type and the leading cause of cancer-associated mortality worldwide. The aim of the present retrospective study was to evaluate the efficacy and safety of computed tomography (CT)-guided 125I brachytherapy alone in elderly patients with NSCLC. A total of 26 elderly patients with NSCLC stage I–III who had an inoperable lesion or progressive disease following radio-chemotherapy were treated with CT-guided 125I seed implantation for lung lesions and included in the present study. The prescribed dose of 125I brachytherapy was 80–140 Gy, and dosimetric verification was performed immediately after the procedure. The response rate (RR) and local control rate (LCR) were analyzed according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Survival was estimated using the Kaplan-Meier method. Safety and complications were also documented. All patients were aged 65–85 years (median age, 77 years) and successfully completed the procedure, and the median follow-up time was 9.4 months (range, 3–31 months). After a 6-month follow-up, for pulmonary lesions, complete response (CR) was achieved in 11 (42.3%) cases, partial response in 9 (34.6%) cases, stable disease in 4 (15.4%) cases and progressive disease in 2 (7.7%) cases. The 6-month RR and LCR were 76.9 (20/26) and 92.3% (24/26), respectively. The mean overall survival (OS) time was 11.7±7.6 months and the 0.5- and 1-year OS rates were 90.1 and 73.3%, respectively. Tumor-related symptoms in patients were significantly alleviated following the procedure. No severe complications occurred during and after the procedure of 125I seed implantation. In conclusion, CT-guided 125I brachytherapy is a feasible, effective and safe therapy and may be considered as an alternative option to surgery and radiotherapy for elderly patients with NSCLC.