Abstract: Objective：To study the predictive value of serum levels of AFP, CA19-9 and WHO histological types for the prognosis of combined hepatocellular carcinoma-cholangiocarcinoma patients after surgery. Methods：From April 1999 to March 2017, 206 patients with cHCC-ICC who underwent curative surgical resection at Zhongshan Hospital, Fudan University were selected. The histological types of cHCC-ICC were reassessed and the clinicopathologic information of each patient was intact. According to the results of immunohistochemistry, pathological results were divided into type Ⅰ and type Ⅱ (Ⅱa, Ⅱb, and Ⅱc). According to the serum level of AFP and CA19-9, 206 cHCC-ICC patients were categorized into 3 groups: double positive group (AFP＋CA19-9－, n=41), single positive group (AFP＋CA19-9－ or AFP－CA19-9－, n=114) and double negative group (AFP－CA19-9－, n=51). The correlation between different clinicopathological features was analyzed. Survival analysis was performed between different groups and histological types. Results：The double-positive group had a shorter overall survival time (OS) compared with the single positive group (P=0.002) or the double-negative group (P=0.008), and the incidence of microvascular invasion was higher than that of the single positive group (P=0.001) and the double negative group (P=0.006); whereas the tumor-free survival time did not differ among the groups. In patients with TNM-ICC stage Ⅰ, histological type Ⅱ a, type Ⅱ c had a shorter disease-free survival time (DFS) than patients with type Ⅰ (P=0.048). No correlation was found between histological types and OS or DFS in other stages. Conclusions：Histopathological classification based on the WHO classification criteria in 2010 has no significant correlation with the prognosis of cHCC-ICC. The combined application of serum AFP and CA19-9 is helpful to forecast the prognostic value of cHCC-ICC.