Histologically node negative esophageal squamous cell carcinoma (pN0 ESCC) after radical resection still carries a significant risk of recurrence, especially in high-risk patients. Our previous study showed that the risk of recurrence was associated with tumor location and cell differentiation, as well as the presence of lymphovascular invasion. Most recurrence occurs within two years after surgery. There is still a lack of knowledge on the risks or potential benefits of postoperative adjuvant therapies for high-risk pN0 ESCC patients. This study was designed to evaluate the efficacy and toxicity of adjuvant therapies after radical surgery in high-risk patients with pN0 ESCC. This study is a multicenter, prospective, controlled randomized trial, which will compare the differences between either adjuvant chemotherapy or adjuvant radiotherapy and surgery alone for high-risk pN0 ESCC. Patients in group A will receive three cycles of adjuvant chemotherapy with paclitaxel and cisplatin, patients in group B will receive adjuvant radiotherapy with intensity-modulated radiation of 50 Gy, and patients in group C (the control) will receive surgery alone. The primary endpoint is three-year disease-free survival. Secondary endpoints include toxicity of adjuvant therapies and five-year overall survival. One hundred and sixty-two patients in each group are required and a total of 486 patients will finally be enrolled into the study. This will be the first randomized trial to investigate the necessity or potential benefit of postoperative adjuvant therapies for high-risk pN0 ESCC patients.