Abstract: Objective: To investigate the clinical efficacy of radioactive iodine-125 interstitial brachytherapy for treatment of middle to late stage lung cancer. Methods: The dose distribution of iodine-125 seeds was assessed by thermoluminescence dosimetry method (TLD) and dose calculation formula. The radial dose of iodine-125 seeds was compared using measured and calculated results. Thirty-eight patients with unresectable middle to late stage lung cancer were treated with interstitial radiation of iodine-125 seed implants. The iodine-125 seeds were implanted into the carcinoma by video adapter thoracoscope (VATS). Results: The experimental results indicated that the effective interstitial space of the seeds was 1cm. After 6 months, the total response rate (CR+PR) was 63.16%, and the symptoms of cough, shortness of breath, decreased appetite and chest pain were obviously reduced after surgery. There was no massive bleeding, pneumothorax, pneumonia or atelectasis after surgery. Conclusion: Radioactive iodine-125 seed implants are safe and effective and might be helpful in the treatment of unresectable middle to late stage lung cancer.