Objective To investigate the effects and molecular mechanisms of TOP2A on the biological be-havior of liver cancer cells.Methods TOP2A-overexpressing cell lines wereestablished and examined using RT-qPCR and Western blot.After overexpression of TOP2A,the proliferation and clonogenoc ability of HepG2 cells were assessed using CCK-8 and clonogenic assays,while flow cytometry was employed to detect cell apop-tosis.Bioinformatics analysis was performed to identify TOP2A-related proteins,and changes in mRNA and protein levels of p53 were detected using RT-qPCR and Western blot afteroverexpression of TOP2A.Expres-sion of apoptosis-related proteins,including Caspase9 and Caspase3,were also detected using Western blot.Re-sults After overexpression of TOP2A,the expression level of TOP2A in cell lines increased significantly(P<0.05).Overexpression of TOP2A significantly increased the proliferation,migration,and clonogenic ability of HepG2 cells,and reduced the cell apoptosis(P<0.05).Bioinformatics analysis showed that there was a close in-teraction between TOP2A and p53.Overexpression of TOP2A significantly inhibited the expression of p53 mR-NA(P<0.05).At the same time,overexpression of TOP2A significantly inhibited the expression of p53,Casepasse9,and Casepasse3 proteins(P<0.05).Conclusion Overexpression of TOP2A may inhibit the p53 mediated signaling pathway,reduce the apoptosis mediated by Caspase9 and Caspase3,and promote the prolifer-ation,migration,and clonal formation of liver cancer cells.