Purpose: To determine the mechanism of action of Tripterygium wilfordii Hook F (TwHF) in the treatment of rheumatoid arthritis (RA) based on network pharmacology and molecular docking. 
 Methods: The active constituents and targets of TwHF were screened by searching the TCMSP, TCMIP, PharmMapper database, and BATMAN-TCM platform combined with oral bioavailability and drug-like analysis. The drug-component-target maps were drawn using the UniProt database and Cytoscape 3.9.0 software. The drug-target maps were searched in GeneCards, OMIM, TTD, PharmGKB, and DrugBank databases to obtain the predicted targets of RA, Venn diagrams were drawn to derive the common targets of TwHF components and RA and protein-protein interaction (PPI) network, GO enrichment as well as KEGG pathway analyses were performed. The potential binding activities between the active constituents of TwHF and the targets were predicted using molecular docking. 
 Results: Seven active components and 131 potential targets were found for TwHF while RA had 4,917 related targets. However, TwHF and RA had 87 common targets. The target genes obtained from the PPI network include tumor necrosis factor (TNF), p53 tumor protein (TP53) and vascular endothelial growth factor A (VEGFA). The GO enrichment and KEGG pathway analysis yielded 336 results and 121 signal pathways, respectively. 
 Conclusion: Tripterygium wilfordii Hook F therapy for RA may be a multi-component, multi-target and multi-signal pathway biological process, which may regulate VEGFA, TNF, TP53 and other targets and also exhibit anti-inflammatory and immunomodulatory functions amongst others. Future studies should determine the relationship of the identified targets in vivo to produce alternative treatments for RA.