This study aimed to analysis outcome and prognosis of interstitial 125I seed implantation in patients with cervical lymph node recurrence after multimodal treatment of thoracic esophageal squamous cell carcinoma (ESCC). We conducted a retrospective review of 19 patients with 32 cervical lymph nodes recurrences after multimodal treatment (lymphadenectomy, radiotherapy, chemotherapy, and various combinations of these treatments) of thoracic ESCC, who underwent 125I seed implantation in our department from 2003 to 2011. All the patients were followed up until expiration and the median duration of follow up was 7 months (range, 3-44 months). Syndromes significantly improved after implantation. The local control rates after 3, 6, 12, and 24 months were 84.2%, 63.2%, 32.0%, and 26.0%, respectively, with a median of 10 months. The median overall survival time was 7 months (95% CI, 5.6-8.4), and 1- and 2-year survival rates were 31.6% and 10.5%, respectively. Among these patients, there were 11 died of progression of disease (PD) 3-44 months after implantation. One patient presented grade IV skin toxic effect and repaired by free flap transplantation. No fatal complications such as massive bleeding happened. In univariate analysis, N stage, number of recurrent nodes, recurrence interval time, and D90 were prognostic factors of the tumor local control and survival (p = 0.131 vs. 0.029, 0.129 vs. 0.071, 0.042 vs. 0.042, and 0.056 vs. 0.065, respectively). Multivariate analysis demonstrated that N stage, number of recurrent nodes, and recurrence interval time were independent prognostic factors of the tumor local control (p = 0.022, 0.019, and <0.001, respectively), and recurrence interval time was prognostic factor of the survival (p < 0.001). Interstitial 125I seed implantation is a safe and effective salvage treatment for cervical lymph node recurrence after multimodal treatment. The N stage, number of recurrent nodes and recurrence interval time are factors influencing tumor local control, and the recurrence interval time is independent factor influencing survival after percutaneous 125I seed implantation in ESCC with cervical lymph node recurrence.