To explore the medication rule and mechanism of Chinese medicine prescriptions in the treatment of knee osteoarthritis with liver and kidney deficiency based on data mining and network pharmacology.Methods:China National Knowledge Infrastructure(CNKI) was searched for the prescriptions for the treatment of knee osteoarthritis with liver and kidney deficiency in the last 10 years.Traditional Chinese Medicine Inheritance Support System was used to establish a database and its entropy clustering algorithm was adopted to summarize the drug frequency，core combination，core drug mode and meridian frequency of the prescriptions for the treatment of knee osteoarthritis with liver and kidney deficiency，and to obtain the new prescription combination.Then Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)，Gene Expression Omnibus(GEO)，STRING and Metascape as well as Cytoscape were employed for the intersection of core drug targets and differentially expressed genes and the construction of protein-protein interaction(PPI) network.Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis was performed and the drug-component-target network diagram was established.Results:A total of 72 prescriptions that met the inclusion criteria were selected for frequency statistical analysis.It was found that there were 25 Chinese medicinal materials with frequency≥10，among which Radix Achyranthis Bidentatae，Radix Angelicae Sinensis and Radix Rehmanniae Preparata were used more frequently，and they belonged to the liver，kidney and spleen meridians.Sixteen core combination drugs and 8 new prescriptions were excavated by hierarchical cluster analysis of entropy clustering.The network pharmacological analysis of the core Chinese medicinal materials Radix Achyranthis Bidentatae，Radix Angelicae Sinensis and Radix Rehmanniae Preparata showed that there were 176 key active components and targets，such as quercetin，stigmasterol and β-sitosterol，and 258 differentially expressed genes of knee osteoarthritis.The core Hub genes were mainly IL-6，MMP9，CXCL8，JUN and VEGFA in IL-17，TNF，Toll-like receptor and NF-κB signaling pathways based on KEGG enrichment analysis.Conclusion:The treatment of knee osteoarthritis with liver and kidney deficiency focuses on tonifying and replenishing the liver and kidney，dredging collaterals and relieving pain.The mechanism may be achieved by acting on IL-6，MMP9 and other targets and regulating the complex pathways such as IL-17，TNF，Toll-like receptor and NF-κB signaling pathways.