Background: Surgery is the main treatment of esophageal squamous cell carcinoma (ESCC), but the prognosis of patients with locally advanced ESCC is rather poor. Preoperative chemoradiotherapy followed by surgery seems to hopefully improve the survival of ESCC. Nevertheless, the results of different studies were inconsistent. We are to carry out a phased III clinical trial to investigate the effect of this multidisciplinary therapy for the overall survival of patients with locally advanced ESCC. Methods: This study is a multi-centered randomized controlled phase III clinical trial. According to Sixth Edition AJCC Cancer Staging, patients with IIB-III staged squamous cell carcinoma of the thoracic esophagus are randomly allocated to either preoperative chemoradiotherapy followed by surgery (arm A), or surgery alone(arm B). The intended number of randomized patients will be 430, 215 per arm. In the arm A, Chemotherapy and radiotherapy are performed concurrently. Patients received two cycles of vinorelbine and cisplatin. Vinorelbine at 25 mg/m² per day is administered in bolus infusion on d1, d8, d22 and d29. Cisplatin at 75 mg/m² is administered by intravenously infusion on d1 and d22 (or 25 mg/m²days 1 to 4 and 22 to 25). A total radiotherapy dose of 40 Gy is delivered in 20 daily fractions of 2.0 Gy each (given 5 d/wk for 4 weeks). McKeown esophagectomy or Ivor Lewis esophagectomy will be performed 4-6 weeks after chemoradiotherapy. Two-field lymphadenectomy with total mediastinal lymph node dissection is performed during sugery. Primary outcomes are 3 and 5 years overall survival. From 2007 July to 2013 December, over 300 eligible patients were randomly assigned in eight cooperative cancer centers. The patient enrollment will be completed in 2014. Clinical trial information: NCT01216527.