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MicroRNAs (miRNAs) are a class of non-coding RNAs 18-25 nucleotides in length, which play important roles in the regulation of cancer progression through gene silencing. miRNA (miR)-101 has been suggested to be associated with hepatocellular carcinoma (HCC). However, the detailed role of miR-101 in HCC metastasis and the underlying mechanism remain largely unclear. The present study demonstrated that the expression of miR-101 was significantly reduced in HCC tissues compared with that in matched normal adjacent tissues. miR-101 was also found to be downregulated in four HCC cell lines compared with its expression in a normal liver cell line. Vascular endothelial growth factor (VEGF)-C was further identified as a direct target of miR-101, and the protein expression of VEGF-C was downregulated by miR-101 in HepG2 HCC cells. Furthermore, the overexpression of miR-101 and the knockdown of VEGF-C significantly inhibited HepG2 cell migration and invasion, while restoration of VEGF-C reversed the inhibitory effect of miR-101 overexpression on HepG2 cell migration and invasion. Finally, the expression of VEGF-C was notably increased in HCC tissues and cell lines. These findings suggest that miR-101 exerts a suppressive effect on HCC cell migration and invasion, at least in part through the direct inhibition of VEGF-C protein expression. Therefore, the miR-101/VEGF-C axis may serve as a potential therapeutic target for HCC metastasis.