In this report, a 63-year-old male patient was admitted due to "dull pain in the right upper abdomen for 2 months". Imaging and pathological examination confirmed the diagnosis of synchronous hepatocellular carcinoma (CNLC Ⅰa stage) and duodenal papillary carcinoma (moderately-poorly differentiated adenocarcinoma complicated with signet ring cell carcinoma). The patient had a history of chronic hepatitis B. After Multidisciplinary team (MDT) consultation, laparoscopic local resection of segment 5 of the liver combined with pancreatoduodenectomy were performed to achieve R0 resection. Liver metastasis occurred 2 months after operation, and it was completely relieved after TACE, tirelizumab immunotherapy and FOLFOX4 chemotherapy. Postoperative survival time has exceeded 16 months. This case of synchronous double primary carcinoma of the liver and duodenal papilla is extremely rare, and it is likely to miss the diagnosis in clinical practice, suggesting that after the diagnosis of one type of malignant tumor, comprehensive evaluation is still needed to exclude other primary lesions. PET-CT shows important value in the early identification of such multiple primary cancers. Through multi-mode strategy of individualized comprehensive treatment and whole-course management, this patient achieved favorable tumor control effect, providing reference for clinical diagnosis and treatment of such rare cases.