Objective: To discuss the experience regarding the diagnosis and treatment of adenosquamous carcinoma of the pancreas so as to improve the knowledge and management of this disease. Methods: The clinical data of 6 patients with adenosquamous carcinoma of pancreas admitted from June 2002 to June 2014 were retrospectively analyzed and discussed with review of the related literature. Results: Of the 6 patients, the lesion was located in the head of the pancreas in 3 cases, and in the body and tail of the pancreas in 3 cases; the average age was 63.3 years. The main symptoms included abdominal pain and yellow urine, and the CA19-9 level was increased in 5 cases. In all of the cases, a space-occupying lesion of the pancreas was suspected by CT and other imaging examinations. Two cases underwent pancreaticoduodenectomy, three cases underwent resection of the body and tail of the pancreas plus splenectomy, and one case had palliative surgery due to involvement of the posterior wall of the stomach and the descending part of the duodenum. Microscopic pathological examination showed that all the tumors consisted of a mixture of adenocarcinoma and squamous cell carcinoma. At postoperative follow-up, 4 cases had died, one case was lost to follow up, and the mean survival time was 21 (7–56) months. Conclusion: Adenosquamous carcinoma of the pancreas is a rare tumor with high malignancy, difficult preoperative diagnosis and poor prognosis. Surgery is still the first therapeutic option for this condition, and its efficacy may be probably improved through combination with radiotherapy and chemotherapy.