Abstract: OBJECTIVE To extract the essential oil of “Wenyujin Rhizoma Concisum-Angelica Sinensis Radix”, and to qualitatively analyze the chemical composition of the extracted essential oil by LC-MS. Network pharmacology was used to explore the mechanism of the essential oil acting on knee osteoarthritis(KOA). METHODS The essential oil of “Wenyujin Rhizoma Concisum-Angelicae Sinensis Radix” was extracted by steam distillation, the components of the essential oil were analyzed by LC-MS. PubChem, Swiss Target Prediction, GeneCards, DAVID and other databases were used to predict disease targets and pathways of active component in prevention and treatment of KOA. The key genes were analyzed by Gene ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Cytoscape was used to construct a visual network map of “active component-disease targets”. AutoDock and Pymol were used to verify the molecular docking between the target with the highest degree target and the active components. RESULTS A total of 59 compounds were identified in the “Wenyujin Rhizoma Concisum-Angelicae Sinensis Radix” essential oil, and the main components were curzerenone, isocurcumenol, ligustilide, etc. Through network pharmacology, 28 potential targets of essential oil acting on KOA were screened, including CTSK, PTGS1, PTGS2 and ESR1, etc. KEGG enrichment analysis predicted that “Wenyujin Rhizoma Concisum-Angelicae Sinensis Radix” essential oil mainly targeted TNF signaling pathway, osteoclast differentiation, IL-17 signaling pathway, relaxin signaling pathway, MAPK signaling pathway to treat KOA. The results of molecular docking showed that the screened active components and their corresponding target proteins had positive binding activity. CONCLUSION LC-MS combined with network pharmacology is used to preliminaries explore the main active components and the potential targets and mechanism of action of “Wenyujin Rhizoma Concisum-Angelicae Sinensis Radix” essential oil in the intervention of KOA, providing ideas for the further study of “Wenyujin Rhizoma Concisum-Angelicae Sinensis Radix” essential oil.