OBJECTIVE External beam radiotherapy combined with brachytherapy was an important treatment regime for local advanced esophageal cancer. The aim of this study was to retrospectively observe and analyze the long-term treatment outcomes and side effect for a total of 708 esophageal squamous cell cancer patients who were treated with Californium-252 (252Cf) neutron brachytherapy (NBT) in combination with external beam radiotherapy (EBRT). METHODS From November 2001 to March 2012,708 patients of esophageal cancer underwent NBT in combination with EBRT. The patient numbers distributed over various cancer stages Ⅰ,ⅡA,ⅡB,Ⅲ and ⅣA were 7,254,31,404 and 12,respectively. The total radiation dose to the reference point via NBT was 8-25 Gy in 2-5 fractions with one fraction per week. The total dose via EBRT was 50-56 Gy delivered over a period of 5-6 weeks with normal fractionation. RESULTS The overall median survival time was 23.6 months. The 1-,3- and 5-year survival rates were 71.6%,41.8%,and 32.1%,respectively. It showed that radiation dose is the only factor that was likely to be associated with the overall survival and local control rates. The 5-year survival rates for radiation dose <60 Gy,60-68 Gy and >68 Gy,were 27.5%,35.3% and 22.1%,respectively (P<0.001). For acute toxicity,no esophageal perforation was found during the treatment period.Totally 97 cases (or 13.7%) developed the Grade Ⅲ toxicity in the blood. A majority of the patients (635,or 89.7%) developed grades 1 and 2 esophagitis during treatment. Among all the patients,18 cases (or 2.5%) and 35 cases (4.9%) were found esophageal perforation and massive bleeding during the follow-up period. Esophagus strictures occurred in 13 patients (or 1.8%) and temporary expansion of the esophagus was needed during treatment. CONCLUSIONS The clinical data showed that NBT in combination with EBRT produced favorable local control and long-term survival rates for patients with esophageal cancer and the side effects are tolerable. We conclude that this dual-modality method is an effective and safe way for treating esophageal cancer. © 2017, Editorial Board of Chinese Journal of Cancer Prevention and Treatment. All right reserved.