Radiotherapy is one of the main treatments for esophageal squamous cell carcinoma, but there are still no biomarkers to differentiate patients who will benefit from radiation. Although treatment with a combination of radiotherapy with chemotherapy, and/or surgery improves the prognosis of patients, no biomarkers can distinguish between the responses obtained with the combined therapies. Therefore, in this study, we selected patients treated with radiotherapy alone to evaluate survivin as a predictor for radiotherapy. One hundred two biopsy samples collected by endoscopy were immunostained by survivin antibody. Positive staining for survivin was obtained in 60.8% tumor samples. Survivin expression, metastasis, and clinical stage correlated significantly with overall survival. In multivariate analysis, survivin was an independent prognostic factor for predicting overall survival of patients with esophageal cancer. Moreover, in esophageal cancer cell lines, overexpression of survivin reduced the percentage of cell death induced by radiation. Our data indicate that survivin could be a potential predictor to define those patients with esophageal squamous carcinoma who would benefit from radiotherapy.