Abstract: Objective：To explore the expression and clinical significance of ubiquitin-like with PHD and ring finger domains 2 (UHRF2) in intrahepatic cholangiocarcinoma (ICC). Methods：The expression of UHRF2 in 138 ICC was determined by immunohistochemistry, and the relationships between UHRF2 expression with prognosis and clinicopathological features of ICC were analyzed. Results：UHRF2 was highly expressed in ICC compared with paratumorous tissues. Level of UHRF2 was associated with high AFP level (P=0.010), poor tumor differentiation (P=0.026), lymph node metastasis (P=0.001), and advanced TNM stage (P=0.019). Elevated UHRF2 expression was suggested to be associated with poor prognosis and high recurrence rate in ICC patients (P<0.001), and multivariable analysis indicated that UHRF2 was of theprognostic indicators of ICC (P<0.05). Conclusions：High level of UHRF2 is related to the malignant phenotype of ICC, and can be a prognostic and recurrent indicator of postoperative patients.