Objective: Various immunohistochemical studies have been performed regarding intrahepatic cholangiocarcinoma (ICC), including the cell cycle-related proteins (p27, cyclin D1, 14-3-3σ, p53, cyclin B1 and Ki-67), the proto-oncogenes (c-erbB-2 and c-Met), the extracellular matrix proteins (tenascin and laminin) and others (β-catenin, epidermal growth factor receptor, osteopontin, aquaporin 1, MUC5AC and fascin). Nevertheless, none of these have been proven to be a predictive power of the prognosis with high specificity and sensitivity for ICC. Methods: Sixty-one patients with ICC were selected and ICC specimens were immunohistochemically stained with the above 16 markers, as previously reported. Results: The immunoreactivity of osteopontin, tenascin and Ki-67 divided the patients with ICC into 4 subgroups by the survival tree model. There was a significant relationship between the location of the tumor, TNM classification, histological differentiation, tumor size, lymphatic permeation, perineural invasion, lymph node metastasis, intrahepatic metastasis and viral infection among the 4 subgroups. In addition, there was a significant difference in survival among the 4 subgroups. Conclusion: In this study, the subgrouping by the survival tree model might be helpful for predicting the patients’ prognosis in ICC.