Abstract: Because of the special anatomical position of hilar cholangiocarcinoma and its characteristics of longitudinal and vertical invasion, it is difficult to obtain satisfactory effect by surgical resection. More and more researchers have realized that the treatment of the hilar cholangiocarcinoma should take biological characteristics of the tumor. Precise medicine using of frontier technologies and omics technologies such as proteomics and genomics, can accurately diagnose diseases at molecular level and may provide a new model for the treatment of hilar cholangiocarcinoma. The gene mutation rate of the hilar cholangiocarcinoma is higher, and the most common mutation genes are KRAS and TP53, following other genes such as CDKN2A, SMAD4, ERBB2, PTEN, APIK3CA, ARID1A, MLL3, ROBO2, RNF43,and PEG3, GNAS, etc. Such frequent, important functional mutations suggest that hilar cholangiocarcinoma may have potential therapeutic targets for molecular targeted drugs. However,due to the complex pathogenesis of the bile duct cancer, the clinical trials of most targeted drugs have not been able to achieve breakthrough progress. Surgical resection should still remain the dominant treatment. The appropriate extent of hepatectomy should be determined individually, and the minor resection is enough for most hilar cholangiocarcinoma.