Objective: To detect the expression of high mobility group protein 1 (HMGB1) and the receptor for advanced glycation end products (RAGE) in the tissues of patients suffering from cholangiocarcinoma, and to study the possible mechanism of HMGB1 and RAGE on the growth and epithelial-mesenchymal transition (EMT) of human cholangiocarcinoma cells. Methods:Immunhistochemical study was performed to analyze the expression of HMGB1 and RAGE in cholangiocarcinoma tissues with or without metastasis; ELISA method was used to detect the level of HMGB1 in the bile of patients with hepatolithiasis and cholangio-carcinoma;The effect of HMGB1 and RAGE on cell proliferation and invasion was detected by CCK8 and Transwell assay; the expression of HMGB1 and p-ERK in tissues of cholangiocarcinoma was detected by Western blot. Results: HMGB1 and RAGE were significantly higher in cholangiocarcinoma tissues with metastasis than in those without metastasis. HMGB1/RAGE can obviously promote the growth of cholangiocarcinoma cell line in vitro and promote the expression of EMT relative cytokines. Conclusion: HMGB1 and RAGE can promote the EMT and proliferation of cholangiocarcinoma cell line