Abstract: Cholangiocarcinoma (CCA) is a common cancer in hepatobiliary system.Because CCA is in sensitive to conventional chemotherapy and radiotherapy,the current treatment is mainly depending on the surgical operation when diagnosed early.Tumor necrosis factor related apoptosis inducing ligand (TRAIL) plays a key role in the process of controlling cell proliferation by binding with its receptor and therefore mediated cell apoptosis.Although the characteristic of selectively killing tumor cells by TRAIL makes it become the new direction of clinical treatment of cancer,the condition that CCA cells are resistant to TRAIL mediated apoptosis restricts its scope of application.Nowadays many studies demonstrate that multiple signaling pathways can regulate the sensitive of CCA cells to TRAIL mediated apoptosis.In this review,we summarize the expression and effects of TRAIL and its receptor in CCA,and conclude the mechanism of multiple pathways restoring the sensitivity of CCA cells to TRAIL mediated apoptosis.