Objective:To detect the expression of WW domain containing oxidoreductase (WWOX) in intrahepatic cholangiocarcinoma (ICC) tissues and cells,to analyze the correlation between WWOX expression and clinical features of ICC,and to investigate its effect on cellular migration and invasion of ICC. Methods:The expression level of WWOX in ICC tissues and cell lines were measured by semi-quantitative real-time PCR and quantitative real-time PCR. The expression of WWOX in ICC cells was overexpressed by recombinant plasmid pcDNA3.1B-WWOX-Flag transfection. The effect of WWOX overexpression on migration and invasion of ICC was performed by wound healing and matrigel invasion assays. The potential signaling molecules involved in migration and invasion was measured by Western blot assay. Results:WWOX was down-regulated in ICC tissues and cell lines,and the downregulated WWOX was significantly associated with the metastasis of ICC (P < 0.05). The expression of WWOX was upregulated by pcDNA3.1B-WWOX-Flag transfection in ICC cells. Overexpression of WWOX inhibited cellular migration and invasion of ICC (P < 0.001). The overexpression of WWOX stimulated the activation of extracellular regulated protein kinases 1/2 (ERK1/2) phosphorylation,which in turn reduced the activity of matrix metalloproteinases 9,resulting in metastasis suppression of ICC. Conclusion:WWOX was down-regulated in ICC,and overexpression of WWOX was proved to inhibit the ability of migration and invasion of ICC cells in vitro.