Iodine-125 (125I) seed-loaded stent placement has served as an effective palliation for malignant esophageal strictures in China. We performed a retrospective study to identify the prognostic factors of this irradiation stent placement in advanced esophageal cancer patients. A total of 201 patients who underwent 125I seed-loaded stent placement were included in this study from June 2012 to March 2016 at five hospitals in China. The Cox regression models adjusted for stratification factors were used, and a stepwise multivariate analysis was performed to predict the overall survival and relief of dysphagia on the basis of pretreatment clinical characteristics, respectively. Three independent prognostic factors were identified for overall survival: histopathological subtype (squamous cell carcinoma vs. adenocarcinoma, hazard ratio [HR] 1.45, 95% confidence interval [CI95%]: 1.01-2.09, P = 0.046), serum total protein (≥66 g/L vs. <66 g/L, HR 0.61, CI95%: 0.48-0.59, P = 0.023), and performance status (<2 vs. ≥2, HR 1.57, CI95%: 1.09-2.08, P = 0.013). Four factors were significantly associated with the relief of dysphagia: T stage (T3 vs. T4, P = 0.003), tumor location (superior vs. inferior, P = 0.049), tumor-node-metastasis classification (IV vs. II, P = 0.025), and age (≥71 years vs. <71 years, P = 0.029). Prognostic factors identified from this analysis can be used to aid clinical decision-making and design future clinical trials.