〔Abstract〕 To explore the role and mechanism of plasmalemma vesicle-associated protein (PLVAP) in the progression of hepatocellular carcinoma (HCC) . Methods Bioinformatic analysis , quantitative real-time PCR , Western blot and immunohistochemistry were used to analyze the expression level of PLVAP in HCC and paracan- cerous tissues , and its correlation with clinicopathological characteristics . Stable HCC cell lines with knockdown and overexpression of PLVAP were constructed , then cell proliferation , migration and invasion of HCC cells were examined by CCK-8 , foci formation assays , wound-healing assays and Transwell assays . Western blot was used to detect the protein levels of phosphatidylinositol 3-kinase PI3K , phosphorylated phosphatidylinositol 3-kinase p- PI3K , protein kinase B AKT and phosphorylated protein kinase B p-AKT in the PI3K/AKT pathway after PLVAP knockdown and overexpression . Cell proliferation , migration and invasion were also examined in PLVAP-overex- pressed cells after treatment of LY294002 , an inhibitor of the PI3K/AKT pathway . Results The expression of PLVAP was significantly higher in HCC tissues than that in adjacent non-tumor tissues (P < 0. 05) , and was posi- tive correlated with tumor Stage , T stage , M stage , and microvascular invasion (P < 0. 05) . Knockdown of PLVAP significantly reduced the proliferation , migration and invasion of HCC cells (P < 0. 001) , while overexpression of PLVAP significantly increased the proliferation , migration and invasion of HCC cells (P < 0. 01) . Western blot a- nalysis revealed that knockdown of PLVAP decreased the protein expression levels of p-PI3K and p-AKT , overex- pression of PLVAP increased the protein expression levels of p-PI3K and p-AKT , whereas the PI3K/AKT inhibitor LY294002 eliminated the effects of PLVAP on cell proliferation , migration and invasion (P < 0. 01) . Conclusion PLVAP is highly expressed in HCC and may promote HCC progression by activating the PI3K/AKT signaling pathway .