AIM: To explore the expression and function of slug, a transcriptional repressor, in human intrahepatic cholangiocarcinoma (IHCC) and identify its role in IHCC progression. METHODS: Expression of slug was detected in 36 cases of IHCC and 12 cases of normal intrahepatic bile ducts and liver parenchyma by immunohistochemistry. The patients were divided into low slug expression group (< 20% of carcinoma cells stained) and high slug expression group (≥ 20% of carcinoma cells stained). Slug expression was correlated with clinicopathological parameters of IHCC patients. The patients were defined as short-term survivors if their survival time was < 12 mo and as longterm survivors if their survival time was ≥ 12 mo. RESULTS: Slug was not expressed in normal liver epithelium samples, lowly expressed in 15 tissue samples (10 -, 5 +) and highly expressed in 21 tissue samples (16 ++; 5 +++) from IHCC patients. The survival rate of patients with a low slug expression was 33.3% (n = 5) and 66.7% (n = 10), respectively. The survival rate of patients with a high slug expression was 61.9% (n = 13) and 38.1% (n = 8), respectively (P = 0.02). Lymph node metastasis was found in 4 (26.7%) out of the 15 patients with a low slug expression and in 14 (66.7%) out of the 21 patients with a high slug expression, respectively. The incidence rate of lymph node metastasis increased with the increasing slug expression level (P = 0.003), and higher in patients with a high slug expression than in those with a low slug expression. Slug expression did not significantly correlate with the tumor size and stage or histologic grade, or with the gender and age of patients. CONCLUSION: Slug expression is a novel prognostic marker for IHCC with lymph node metastasis.