Objective To explore the main active components and potential mechanism of Tripterygium Wilfordii in the treatment of liver cancer by network pharmacology and molecular docking technique. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to screen the main active components and targets of Tripterygium Wilfordii; Drugbank, Genecards, OMIM and TTD database were used to screen liver cancer targets; The therapeutic target of Tripterygium Wilfordii for liver cancer was mapped by R language and drawing Venn diagram, the PPI network graph of the therapeutic target was constructed by STRING, Cytoscape was used to construct the interaction network of “Tripterygium Wilfordii-active components-target-liver cancer”; The Go function and KEGG pathway were analyzed by R language software; PubChem, RCSB PDB database, AutoDock and PyMOL software were used for molecular docking between potential components and key targets. Results A total of 51 active components and 120 potential therapeutic targets were selected, which mainly involved the biological processes of amide binding, peptide binding and DNA-binding transcription factor binding, it is mainly concentrated in the signal pathways of Kaposi sarcoma-associated herpesvirus infection, hepatitis B, fluid shear stress and arteriosclerosis. Molecular docking verification showed that the docking score was more than-5kcal/mol accounted for 100%, which means that all the targets had high docking activity with the components. Conclusion Through the network pharmacology method and molecular docking technology, we have confirmed the action characteristics of Tripterygium Wilfordii multi-component, multi-target, multi-pathway, and predicted the potential mechanism of Tripterygium Wilfordii in the treatment of liver cancer, it provides a theoretical basis for further development and application.