Abstract: OBJECTIVE To study the molecular mechanism of couple medicine of Dipsaci Radix-Psoraleae Fructus for the treatment of osteroarthrits(OA) based on network pharmacology. METHODS The Chinese Medicine System Pharmacology Analysis Platform(TCMSP) was used to search for all chemical constituents and related targets. The OMIM database, DrugBank database and GeneCards database were used to find OA-related targets. The bioactive compound-target network was established by Cytoscape 3.7.1 software. The screened targets were used to construct the protein-protein interaction(PPI) network of Dipsaci Radix, Psoraleae Fructus and couple medicine of Dipsaci Radix-Psoraleae Fructus treating OA on the STRING V10.5 platform. The network topological parameters were used to screen out the hub genes and Clusterprolifer in R was employed to perform Gene Ontology(GO) analysis and KEGG pathway enrichment analysis on hub targets. RESULTS Used the oral bioavailability ≥ 30% as screening condition for the compounds, combined with supplement literatures searched, 20 active components and 473 corresponding potential targets of couplet medicine of Dipsaci Radix-Psoraleae Fructus. The network topological characteristic parameters, such as Degree, Betweenness, and Closeness were used to screen out 19 hub targets for the treatment of OA. A total of 121 enrichment results were obtained from 19 hub genes of couplet medicine of Dipsaci Radix-Psoraleae Fructus in OA, included 67 biological processes, 45 molecular functions, and 9 cell compositions. The hub genes were enriched by KEGG and 89 pathways played an important role in OA were screen out. CONCLUSION Compared with the signle traditional Chinese medicine, the synergetic effect of couplet medicine of Dipsaci Radix-Psoraleae Fructus with more multi-component, more multi-target, more multi-pathway is confirmed by network pharmacology, which lay a foundation for developing a new drug for the treatment of OA from the couplet medicine of Dipsaci Radix-Psoraleae Fructus.