Objective To assess the short-term clinical efficacy and safety of radioactive ¹²⁵I sealed seed implantation in the treatment of local recurrence of thymoma. Methods A total of 42 patients with local recurrence of thymoma received ¹²⁵I sealed seeds brachytherapy in Huadong Hospital affiliated to Fudan University during Jan. 2015 and Dec. 2018. Surgical complications and postoperative radiation injuries were observed. Computed tomography (CT) scan was used to evaluate the change of tumor size, and then to calculate the tumor volume and the objective response rate before and after treatment. The local pain was evaluated by numerical rating scale (NRS) and the pain remission rate was calculated. Results All the 42 patients successfully received the operation. Low fever occurred in two patients, pneumothorax occurred in one patient, and local skin grade Ⅰ radiodermatitis occurred in two patients after implantation. No other adverse events occurred. The tumor volume was (37.2±8.4) cm³ before treatment, and it was (18.6±4.2), (15.3±4.0) and (14.9±3.7) cm³ at 2, 4 and 6 months after treatment, respectively. The objective response rate was 95.2% (40/42) at 6 months after treatment. Twenty-four patients had local pain before treatment, the median NRS score was 4 (1-9), and the NRS score decreased to 1 (0-6), 1 (0-5) and 1 (0-5) at 2, 4 and 6 months after treatment, respectively. The pain remission rate was 87.5% (21/24) at 6 months after treatment. Conclusion Radioactive ¹²⁵I sealed seed implantation is a safe and effective method in the treatment of local recurrence of thymoma, with a good short-term clinical efficacy and fewer complications.