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Objective:To study the mechanism of Yuanhuzhitong decoction for the treatment of osteoarthritis from the perspective of network pharmacology. Methods:The active ingredients of Yuanhuzhitong decoction were screened out from the TCMSP database,and then the targets of the active ingredients were extracted. The drug-ingredient-target network was constructed using Cytoscape software. The genes of osteoarthritis were obtained by OMIM,GeneCards and DisGeNET databases. Drug targets and disease targets were mapped together,and the relationship of the key target protein-protein interaction (PPI) was obtained through the online STRING database. Key targets were analyzed by Clue GO plug-in for GO functional enrichment and KEGG signaling pathway enrichment. Results:A total of 71 active ingredients and 99 unique targets of alkaloids,coumarins,volatile oils,steroids,etc were obtained through the threshold of OB 30％ and DL 0.18. 45 common targets were obtained through Venn diagram,among which the core targets were IL6,VEGFA,CASP3,CCND1,ESR1,etc. GO enrichment analysis revealed that the biological processes of Yuanhuzhitong decoction for OA were mainly concentrated in cell migration,differentiation,nucleotide metabolism and synthesis,regulation of pri-miRNA transcription by RNA polymerase II,and apoptosis. KEGG analysis showed that Yuanhuzhitong decoction may act on HIF-1 signal pathway,TNF signal pathway,NF-κB signal pathway and other pathways. The results showed that the main active ingredients in Yuanhuzhitong decoction could play an important role for the treatment of osteoarthritis through multi-component,multi-target and multi-pathway. Conclusion:This study analyzed the main active ingredients,key targets,signaling pathways and mechanism of Yuanhuzhitong decoction from the perspective of network pharmacology,laying a foundation for further exploration of its mechanism.