Objective To explore the potential therapeutic targets and mechanisms of Shujinxi External Granules in the treatment of osteoarthritis(OA).Methods The chemical constituents and targets of Shujinxi External Granules were collected from TCMSP,TCMIP,TCMID and HERB databases,and the target genes related to OA were obtained from GEO database.Screening the overlapping targets,Cytoscape software was used to construct the"Shujinxi External Granules-compounds-OA-targets"and protein-protein interaction(PPI)networks.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the overlapping targets through DAVID database,and the compounds and proteins with the highest degree values were selected for molecular docking by using AutoDock Vina.Results There were 85 components and 915 targets were found in Shujinxi External Granules.The 4 383 targets of OA were obtained,and 248 overlapping targets were screened out between Shujinxi External Granules and OA.The key target proteins were epidermal growth factor receptor(EGFR),cyclin-dependent kinase 1(CDK1),matrix metalloproteinase 9(MMP9),and the key compounds were N-trans-feruloyltyramine,palmatine,balanophonin,aurantiamide acetate,Saroaspidin A,luteolin,schizandrin,rhynchophylline,rhynchophylline A,kaempferol,1-piperoylpiperidine.A total of 489 biological processes,162 cellular components and 87 molecular functions were obtained by using GO functional enrichment analysis,and 100 signaling pathways related to the therapeutic of Shujinxi External Granules were obtained by using KEGG pathway enrichment analysis.The molecular docking results showed that N-trans-feruloyltyramine,1-piperonoylpiperidine and rhynchophylline A had good binding ability to the key targets EGFR,CDK1 and MMP9,respectively.Conclusion The Shujinxi External Granules may bind to the key targets EGFR,CDK1,and MMP9 in the pathways in cancer,hypoxia-inducible factor 1(HIF-1)and calcium signaling pathway through the key active components,such as N-trans-feruloyltyramine,rhynchophylline A,and 1-piperoylpiperidine,to exert the therapeutic effects on OA.