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HCC is the leading type of the malignant liver tumors with the unsatisfied prognosis.Liver resection has been considered as the predominant curative therapy,however,the post-surgical prognostic evaluation remains an urgent problem and the mechanism of HCC metastases has not been understood completely.EDG2 has been found to accelerate tumor progression through mediating different cell pathways,however,it has been unclear about the role of EDG2 on HCC pathogenesis.In this study,EDG2 expression was found aberrantly increased in HCC tissues by immunohistochemistry and comparison of survival curves revealed increased EDG2 expression in HCC tissues was associated with the worse prognosis after liver resection.The positive correlation between EDG2 and EMT was observed in HCC samples.Furthermore,EDG2 over-expression in HCC cells brought the typical characteristics of EMT phenotype including up-regulation of Vimentin,Fibronectin and N-cadherin,suppression of E-cadherin,and enhanced cell migration and invasion capacities.EDG2 knockdown experiments reversed the EMT phenotype of HCC cells.The in vivo experiments also identified the oncogenic role of EDG2 on HCC growth.The mechanistic studies elucidated that EDG2 enhanced mTOR phosphorylation via PI3K/AKT signaling and consequently induced EMT of HCC cells.Moreover,EDG2 was found to promote cell viability and proliferation of HCC cell through PI3K/AKT/mTOR/Skp2/p27Kip1 signaling.The data here demonstrated EDG2 is a potential predictor for HCC patients receiving liver resection and accelerates HCC progression via regulating EMT driven by PI3K/AKT/mTOR signaling.