Objective: To investigate the early diagnosis and surgical treatment of cancer of the duodenal papilla. Methods: The clinical data of 80 patients with cancer of the duodenal papilla treated in Xiangya Hospital of Central South University from March 2010 to March 2017 were retrospectively analyzed. Of the patients, 16 cases underwent local resection and 64 underwent pancreatoduodenectomy (PD). Results: The main initial clinical manifestations included pruritus and jaundice in 60 cases (75.0%), abdominal pain and discomfort in 40 cases (50.0%), chills and fever in 4 cases (5.0%), inappetence and emaciation in 3 cases (3.75%), and mass at the duodenal papilla found by examinations in 2 cases (2.5%). The positive rates of preoperative ultrasound, CT, MRI, gastroscope/duodenal endoscope and ERCP were 82.26%, 89.66%, 91.3%, 93.75%, 94.29%, respectively. Among the patients undergoing local resection, 13 cases were adenocarcinoma of the duodenal papilla, one case was neuroendocrine carcinoma of the duodenal papilla and 2 cases were local canceration of duodenal papilla adenoma; among those undergoing PD, 61 cases were adenocarcinoma of the duodenal papilla, 2 cases were neuroendocrine carcinoma of the duodenal papilla and one case was local canceration of duodenal papilla adenoma. In patients undergoing local resection compared with those undergoing PD, the average intraoperative blood loss, hospitalization cost and incidence of postoperative complications were significantly reduced (all P<0.05), but the average length of hospital stay showed no significant difference (P>0.05), and postoperative 1-, 3- and 5-year survival rates also showed no significant difference (all P>0.05). Conclusion: For cancer of the duodenal papilla, duodenoscopy and ERCP are relatively reliable diagnostic methods, and PD should be the first choice of treatment options. For some special cases, local resection can be used as a safe and effective surgical method based upon the premise of strict adherence to indications and ensuring the negative margins during operation.