Objective To investigate safety and therapeutic effect of total pancreatectomy plus splenectomy for patient with pancreatic cancer. Methods The preoperative clinical data, surgical treatment, and postoperative conditions of 1 patient with pancreatic cancer who underwent the total pancreatectomy plus splenectomy in the Affiliated Hospital of Qinghai University in January 2018 were retrospectively analyzed. Results Combination of the patient clinical history, physical examination, laboratory and radiologic results, the patient was diagnosed with the pancreatic cancer. Then the patient underwent the Whipple procedure. During the operation, it was found that the texture of the pancreas was hard, and the spleen arteriovenous were considered to be invaded, and the multiple frozen section analysis during the operation showed that the surgical margin was positive. Eventually, the total pancreatectomy plus splenectomy was performed. The postoperative pathological analysis results revealed to the well-moderately differentiated tubular adenocarcinoma. When the condition of patient became stable, the pancreatin and insulin were required for long time. No severe complications occurred. The patient survived well after the surgery and no recurrence was observed for following-up of 3 months. Conclusion With improvement of surgical techniques and enhancement of postoperative management, total pancreatectomy can be used as a treatment for pancreatic cancer and it is still safe and feasible.