To explore the effective material basis and mechanism of bupleurum-rhubarb in the treatment of cholelithiasis based on network pharmacology and molecular docking technology.Methods:TCMSP database was used to retrieve the active ingredients and potential targets of bupleuri and radix; GeneCards,CTD and TTD databases were used to find the targets related to cholelithiasis.The interaction networks of PPI and Chinese medicine-components-disease-target were constructed with Cytoscape 3.7.2 software and STRING database.DAVID 6.8 database and R 4.0.3 software were used for enrichment analysis of GO and KEGG on mutual targets of drug and disease.AutoDockTools 1.5.6 software was used to verify molecular docking.Results:A total of 23 major active compounds and 91 component targets were screened from the bupleurum-rhubarb pair,and 35 common targets were obtained by crossing 936 cholelithiasis related targets.GO analysis showed that the core targets had biological processes,such as positive regulation of nitric oxide biosynthesis,cellular response to lipopolysaccharide,and positive regulation of smooth muscle cell proliferation.KEGG pathway analysis found that the core target may be related to cancer signaling pathway,HIF-1 signaling pathway and TNF signaling pathway.Molecular docking results showed that stigmasterol had a strong binding activity to TNF(-7.79 kcal/mol),a good binding activity to Jun(-5.71 kcal/mol),and a mild binding activity to TP53(-4.34 kcal/mol).Conclusion:Stigmasterol,quercetin,kaempferol and other active components in bupleurum-rhubarb pair may regulate inflammatory cytokines and hypoxia signal transduction pathway through TNF,Jun,TP53 and other core targets in the treatment of cholelithiasis.