Background :Evidence is accumulating that long non-coding RNAs (lncRNAs) are involved in human tumorigenesis and dysregulated in many cancers, including hepatocellular carcinoma (HCC).Maternally-expressed gene 3 (MEG3) is a lncRNA overexpressed in HCC cells that inhibits HCC progression; however, the mechanism through which MEG3 exerts its oncogenic activity remains largely unknown.Methods: To explore the underlying regulation mechanism of MEG3, the interaction between gene and gene was examined using a luciferase reporter assay.Expression levels were selectively altered in HCC cells and by transfection of MEG3 or antisense nucleic acids for miR-664.Relative expression levels were detected by RT-PCR, The proliferation inhibition of cells were detected by CCK-8 assay ,the protein expression levels were detected by Western blot,Promoter Binding TF Profiling Plate array and Chromatin immunoprecipitation (ChIP) assay were used to comfirm the transcript factors binding to promoter region of MEG3.Results:we demonstrated that MEG3 is down-regulated in HCC tissues.MEG3 over-expression imposes another level of post-transcriptional regulation, whereas MEG3 overexpression reduces the expression of the miRNA-664 target gene, ADH4, through competitive sponging miRNA-664.In addition, NF-KB may affect transcription of MEG3 by directly binding to the promoter region.Conclusion:Our data revealed that NF-KB may affect the transcript of MEG3.MEG3 overexpression inhibited the proliferation of HCC cells, at least in part by affecting miRNA-664-mediated regulation of ADH4.Together,these results suggest that MEG3 is a suppressor of tumor which acts in part through spongingmiR-664.