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Intrahepatic cholangiocarcinoma(ICC)arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer.The overexpression of COUP-TFII has been observed in several types of malignancies.However,its role in ICC progression remains unclear.In this study,we found that the protein level of COUP-TFII was increased,but the mRNA level was unchanged in ICC tissues.High protein expression was positively associated with tumor size,lymph node metastasis,and poor prognosis in ICC patients.Furthermore,the overexpression of COUP-TFII promoted the proliferation,migration,and invasion of ICC cells in vitro and enhanced tumor growth and metastasis in nude mouse models.Mechanistic studies revealed that COUP-TFII induced epithelial-to-mesenchymal transition in ICC cells by upregulating Snail expression.More-over,the activation of PI3K/AKT signaling led to the upregulation of COUP-TFII protein expression in ICC.Together,these findings indicate that COUP-TFII promotes epithelial-to-mesenchymal tran-sition and metastasis in ICC and suggest that this protein is a potential target for adjuvant therapy for these patients.