In the current study, using gene expression profiling analysis we discovered a lncRNA HOXD-AS1 was upregulated in HCC and significantly correlated with poor prognosis of HCC patients. Meanwhile, we demonstrated that HOXD-AS1 promoted HCC metastasis by acting as a ceRNA to upregulate the expression of SOX4 and activated the expression of EZH2 and MMP2, two direct target genes of SOX4.In this study, we found that HOXD-AS1 was significantly upregulated in HCC tissues. Clinical investigation demonstrated high expression level of HOXD-AS1 was associated with poor prognosis and high tumor node metastasis stage of HCC patients, and was an independent risk factor for survival. lncRNAs also can function as competing endogenous RNAs (ceRNAs) by competitively binding miRNAs, thereby modulating the derepression of miRNAs targets.