MiR-381-3p is involved in the occurrence and development of various tumors.However, its biological roles in hepatocellular carcinoma (HCC) is still unknow.Here, we investigated the effects of miR-381-3p in HCC.qRT-PCR was used to detect the expression of miR-381-3p in HCC tissues and adjacent normal tissues.Results showed that miR-381-3p was down-regulated in 94 cases of HCC tissues.Clinical characteristics analysis showed that miR-381-3p expression was associated with gender, CA199, tumor size and metastasis of HCC patients.The expression level of miR-381-3p in SMMC-7721 HCC cells was regulated by transfection, and the effects of miR-381-3p on the function of HCC cells were detected by MTT proliferation assay, transwell assay and wound healing assay.And results showed that miR-381-3p inhibited the proliferation, invasion and migration of SMMC-7721 HCC cells.Multiple databases were used to predict the target genes of miR-381-3p, and GO enrichment analysis and KEGG pathway enrichment analysis were performed on these potential target genes by DAVID online analysis.The databases predicted 854 possible target genes of miR-381-3p, and analyzed their enrichment in three aspects of biological process, cellular component and molecular function.The strongest enrichment of KEGG pathway is the signaling pathways regulating pluripotency of stem cells.miR-381-3p inhibits HCC cell proliferation, invasion and migration and may be a new therapeutic target for HCC.