Compared with conventional radiation, a single-fraction dose and total dose of target volume can be increased in stereotactic body radiation therapy (SBRT). In addition, doses of organs at risk would be reduced, thus effectively improving local control rates and reducing radiation related toxicity. Shorter courses of SBRT also enhance patients' compliance and render the initial of other treatment on schedule possible. Nevertheless, there are few studies focusing on S-1 combined with SBRT for locally advanced pancreatic cancer. Hence, efficacy of combination of S-1 and SBRT needs to be further confirmed. Based on our experience in treating locally advanced pancreatic cancer, SBRT combined with S-1 as the initial treatment for locally advanced pancreatic cancer is proposed to evaluate its clinical efficacy.