Objective: To investigate the Snail expression in intrahepatic cholangiocarcinoma (ICC) and its relations with clinicopathologic features and prognosis of the patients. Methods: The clinical and follow-up data of 55 ICC patients undergoing surgical treatment between December 1999 and January 2010 were retrospectively analyzed. The Snail expressions in specimens of tumor and adjacent tissues from these patients were determined by immunohistochemical staining, and the relations of Snail expression with the clinicopathologic characteristics and prognosis of the patients were statistically analyzed. Results: In tumor tissues compared with their adjacent tissues, both the expression level (2.764 vs. 0.914) and high expression rate of Snail (48.6% vs. 18.0%) were significantly increased (both P<0.05), and Snail expression was significantly associated with the tumor differentiation (χ2=4.231, P=0.040), TNM stage (χ2=6.631, P=0.010), lymphatic metastasis (χ2=4.134, P=0.042), microvascular invasion (χ2=10.197, P=0.001) and recurrence (χ2=4.610, P=0.032); the postoperative overall survival rate was decreased (P=0.018) and accumulative recurrence rate was increased (P=0.032) in patients with high Snail expression compared with those with low expression. Results of univariate and multivariate Cox regression analysis revealed that microvascular invasion, lymphatic metastasis and Snail expression were independent influential factors for prognosis of the patients (all P<0.05). Conclusion: Snail expression is increased in ICC tissue, and its overexpression is closely related to malignant pathological profiles and dismal prognosis of the ICC patients.