Background: To assess the efficacy and prognosis of computed tomography (CT)-guided 125I radioactive seeds implantation brachytherapy (RSI-BT) for recurrent nasopharyngeal carcinoma (NPC) after external beam radiotherapy (EBRT). Methods: Thirty-one patients with recurrent NPC (forty-one lesions) after EBRT from February 2003 to January 2019 were enrolled in this retrospective study. The work-follow of CT-guidance RSI-BT was: indication selection, patient set-up and immobilization on CT couch, CT-simulation, preoperative planning, prescription doses (PD) definition of 110-160Gy, seed implantation, postoperative dosimetric evaluation and postoperative follow-up. Median radioactivity of RSI was 0.43 (range 0.22-0.79, average 0.61) mCi. Median actuarial number of 125I seeds was 24 (range 3-83, average 37). Median value of post-operative D90 was 118.5 (range 62.4-246, average 136.2) Gy. Local control (LC) and overall survival (OS) were investigated for their relationship with the prognosis. The adverse events were evaluated by the Radiation Therapy Oncology Group (RTOG) classification criteria. Results: Median follow-up was 41.9 (range 2.1-60.2, average 44.1) months. Median LC was 35.8 (range 2.1-60.2, average 34.9) months. LC at 1-, 3- and 5-year was 71.3%, 41.9% and 27.9%, respectively. Median OS was 22.6 (range 2.1~60.2, average 27.1) months. OS at 1-, 3- and 5-years was 57.7%, 23.8% and 11.9%, respectively. Univariate analysis suggested that sex (P=0.037) and frequency of previous EBRT (P=0.001) were prognostic factors influencing LC. Moreover, univariate analysis also suggested that frequency of previous EBRT (P=0.012) was prognostic factors influencing OS. Prevalence of side effects (≥grade 3) was 6.5%. Conclusion: 125I RSI-BT was a safe and feasible salvage treatment for recurrent NPC after EBRT. Key words: recurrent nasopharyngeal carcinoma; External beam radiotherapy; 125I seed implantation brachytherapy; overall survival; local control; side effects.