To investigate the expressions of casein kinase II β (CK2β) and X-Linked inhibitor of apoptosis protein (XIAP) in cholangiocarcinoma (CCA) and evaluated their correlations with major clinicopathologic features and patients' survival. Fifty CCA specimens and 20 normal liver tissues were included in the study. Immunohistochemical staining was used to determine the expression levels of CK2β, XIAP in normal and CCA tissues. The relationships of CK2β and XIAP expressions with clinicopathologic parameters and clinical outcome were evaluated. High immunostaining of CK2β and XIAP were observed in 66% (33/50) and 68% (34/50) of CCA tissues, which were significantly higher than that of normal liver tissues 0% (0/20) and 25% (5/20). The high expression of CK2β was significantly associated with TNM stage (P = 0.036), histological grade (P = 0.020) and high serum CEA level (P = 0.010), while high expression of XIAP was only associated with TNM stage (P = 0.014) and high serum CEA level (P = 0.001). By univariant analysis, patients with high expression of CK2β and XIAP demonstrate significantly poorer overall survival (P = 0.003 vs P = 0.018). Cox regression model showed that positive expression of CK2βis an independent factor of prognosis (P = 0.004). The expressions of CK2β and XIAP in CCA tissues showed strong correlations with the tumor progression, CK2β may be applied as a potential prognostic marker for CCA.