ObjectiveTo detect expression of FXYD6 protein in hilar cholangiocarcinoma tissues and explore its significances. MethodsThe expressions of FXYD6 protein in the 58 hilar cholangiocarcinoma tissues and 30 normal bile duct tissues adjacent to cancer were detected by strept avidin-biotin complex (SABC) immunohistochemistry. The relation between FXYD6 protein expression and biological characteristics of patient with hilar cholangiocarcinoma was analyzed. ResultsThe positive rate of FXYD6 protein expression in the hilar cholangiocarcinoma tissues was significantly higher than that in the normal bile duct tissues adjacent to cancer[75.9% (44/58) versus 33.3% (10/30), χ2=15.084, P=0.000]. Furthermore, the positive rate of FXYD6 protein expression in the well and moderately differentiated hilar cholangiocar-cinoma tissue was significantly higher than that in the poorly differentiated hilar cholangiocarcinoma [85.4% (35/41) versus 52.9% (9/17), χ2=5.243, P=0.022], which was not related to the gender (χ2=0.000, P=1.000), age (χ2=1.248, P=0.264), T stage (χ2=0.466, P=0.495), lymph node metastasis (χ2=0.357, P=0.550), pathological stage (χ2=0.005, P=0.944), and perineural invasion (χ2=3.016, P=0.082). Conclustion The positive rate of FXYD6 protein expression is associated with differentiation of hilar cholangiocarcinoma, which might be a new biomarker of it.