OBJECTIVE： To investigate the effects of tangeretin on in vitro proliferation and invasion of human hepatocellular carcinoma HepG2 cells， and to investigate its mechanism. METHODS： After treated with 0 （blank control group）， 10， 20， 40， 60， 80 μmol/L tangeretin for 24， 48 h， the rate of cell proliferation was detected by CCK-8 assay， and IC50 was calculated. After treated with 0， 20， 30 μmol/L tangeretin for 48 h， Transwell invasion test was used to investigate the effects of tangeretin on cell invasion. The effects of tangeretin on mRNA and protein expression of E-cadherin， N-cadherin， Vimentin， Notch-1， CD44 and MMP-9 were determined by RT-PCR and Western blot assay. The phosphorylation of Akt and GSK-3β were investigated by Western blot assay. RESULTS： 10-80 μmol/L tangeretin significantly inhibited in vitro proliferation of human hepatocellular carcinoma HepG2 cells in time and dose-dependent manner； proliferation rates of them were significantly lowered， compared to blank control group （P＜0.05）； IC50 were 55.7， 23.4 μmol/L after treated for 24， 48 h. After treated with 20， 30 μmol/L tangeretin for 48 h， cell invasion was inhibited in HepG2 cells； mRNA and protein expression of N-cadherin， Vimentin， Notch-1， CD44 and MMP-9 decreased significantly， while those of E-cadherin increased significantly； the phosphorylated levels of Akt and GSK-3β increased； there was statistical significance between them and blank control group （P＜0.05）. CONCLUSIONS： Tangeretin can inhibit in vitro proliferation and invasion of human hepatocellular carcinoma HepG2 cell， which may be associated with inhibiting the expression of CK44 and MMP-9 and signal pathway of upstream Akt-GSK-3β through up-regulating the expression of Notch-1 and inhibiting epithelial-mesenchymal transition.