Objective:To investigate the effects and mechanisms of glycyrrhetinic acid(GA)on the proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)of hepatocellular carcinoma SMMC-7721 cells by regulating the β-catenin/transcription factor 4(TCF4)signaling pathway.Methods:HCC cells SMMC-7721 were randomly separated into the control,L-GA,M-GA,H-GA groups(50,100,200 μmol/L GA)and the GA+LiCl group(200 μmol/L GA+40 μmol/L β-catenin activator LiCl).The effects of GA on the proliferation,migration,invasion and apoptosis of SMMC-7721 cells were detected by plate cloning,Transwell experiment and flow cytometry.WB was applied to detect the effects of GA on the expressions of β-catenin/TCF4 signaling pathway proteins(β-catenin、TCF4)and EMT(E-cadherin,vimentin)-related proteins in SMMC-7721 cells.The model of SMMC-7721 cell transplanted tumor in nude mice was established to observe the effects of GA on the growth of transplanted tumor and the expressions of β-catenin and TCF4 proteins.Results:Compared with the control group,SMMC-7721 cell clonal number,migration and invasion numbers,β-catenin,TCF4 and vmentin protein expressions in the L-GA,M-GA and H-GA groups decreased significantly(all P<0.05),while the apoptosis rate and the expression of E-cadherin protein increased(all P<0.05).Compared with the H-GA group,the numbers of clones,migration and invasion,β-catenin,TCF4 and vimentin protein expressions in the GA+LiCl group increased significantly(all P<0.05),while the apoptosis rate and E-cadherin protein expression decreased significantly(all P<0.05).Tumor-bearing nude mouse model experiment showed that the tumor weight and volume and the positive rates of β-catenin and TCF4 proteins in the GA group were significantly lower than those in the control group(all P<0.05).Conclusion:GA can significantly inhibit the proliferation,migration,invasion,and the EMT process of SMMC-7721 cells,thereby inhibiting the progression of HCC.Its mechanism may be achieved by inhibiting the β-catenin/TCF4 signaling pathway.