In Western countries, the standard treatment for locally advanced rectal cancer is preoperative chemoradiotherapy followed by total mesorectal excision. However, in Japan, the treatment results without preoperative chemoradiotherapy are by no means inferior; therefore, extrapolation of the results of preoperative treatment in Western countries to Japan is controversial. We consider that survival may be improved by preoperative chemoradiotherapy with new anticancer agents as they are expected not only to decrease the local recurrence rate but also to prevent distant metastases. We are conducting a multicentre Phase II study to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy using S-1 in patients with locally advanced rectal cancer. The primary endpoint is the rate of complete treatment of neoadjuvant chemoradiotherapy. Secondary endpoints are the response rate of neoadjuvant chemoradiotherapy, short-term clinical outcomes, rate of curative resection and pathological evaluation. The short-term clinical outcomes are adverse events of neoadjuvant chemoradiotherapy and surgery-related complications. Thirty-five patients are required for this study.