Objective: To Analysis the expression of ME3 in hepatocellular carcinoma(HCC)tissues and cell lines, and explore the effect of ME3 on the proliferation, migration and invasion of HCC cells and its underlying mechanism. Methods: The Cancer Genome Atlas(TCGA)was used to define the expression level of ME3 in HCC tissues. RT-PCR and Western blot were performed to detect the mRNA and protein expression level of ME3 in HCC cells. ME3 was knocked down or overexpressed in HCC cell lines. The effects of ME3 on the proliferation, migration and invasion of HCC cells were detected by CCK-8 assay, colony formation assay, transwell assay and BD Matrigel invasion assay. The activity of PI3K,p-AKT and AKT was detected by Western blot. Results: Compared with adjacent normal tissues and liver cells,ME3 was significantly up-regulated in HCC tissues and cell lines. Knockdown of ME3 markedly inhibited the ability of proliferation, migration and invasion in HCC cells,while Overexpression of ME3 resulted in the opposite effects. Furthermore, we found that the activity of PI3K/AKT signal pathway was significantly promoted by ME3. Conclusion: Expression of ME3 is up-regulated in HCC. Moreover, ME3 promotes the proliferation, migration and invasion of HCC cells,and may function as an oncogene in HCC by activating the PI3K/AKT signal pathway．