Objective：To analyze the expression of malic enzyme 3（ME3）in hepatocellular carcinoma（HCC）tissues and celllines， and explore the effects of ME3 on the proliferation，migration，and invasion of HCC cells，as well as its underlying mechanism. Methods：The Cancer Genome Atlas（TCGA）database was used to study the expression of ME3 in HCC tissues. RT - qPCR and Western blot were performed to detect the mRNA and protein expression levels of ME3 in HCC cells. After knocking down or over expressing ME3 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 invasion assay. Western blot was used to detect the expression of proteins related to the PI3K/AKT signaling pathway. Results：Compared with adjacent normal tissues and normal liver celline，ME3 was significantly up-regulated in HCC tissues and cell lines. Knockdown of ME3 markedly inhibited the ability of proliferation，migration and invasion of HCC cells，while overexpression of ME3 resulted in the opposite effects. Furthermore，we found that the activity of PI3K/AKT signaling pathway was significantly activated by ME3. Conclusion：ME3 is highly expressed in HCC tissues，promoting the proliferation， migration and invasion of HCC cells，and may function as an oncogene in HCC by activating the PI3K/AKT signaling pathway．