To explore the mechanism of Shentong Zhuyu Decoction against lumbar disc herniation(LDH) by means of network pharmacology.Methods:The active components of the medicinals in the decoction were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and chemical databases，and the targets of the active component were predicted by SwissTargetPrediction.LDH-related targets were searched from GeneCards，Online Mendelian Inheritance in Man(OMIM)，and DisGeNET，respectively.Thereby，the common targets of the disease and the decoction were screened out，which were the potential targets of the decoction against LDH.Cytoscape was employed to construct the Chinese medicinal-chemical component-common target network，and String to analyze the protein-protein interaction(PPI) and screen key targets.Cytoscape was adopted to construct the network，followed by the Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of key targets by DAVID.Thereby，the mechanism was preliminarily revealed.The nucleus pulposus cells were classified into the simple pressure group and the Chinese medicine group(with the intervention of Shentong Zhuyu Decoction-containing serum) and placed in a hydrostatic pressure loading device for intervention under 1 MPa pressure for 2，4，and 6 h，separately.Apoptosis of nucleus pulposus cells was detected with a kit，and expression of nuclear factor kappa B(NF-κB) p65，matrix metalloproteinase-13(MMP-13)，and cysteine-aspartic acid protease(Caspase3) in the cells by Western Blotting.Results:A total of 121 active ingredients and 871 targets of Shentong Zhuyu Decoction，438 LDH-related targets，75 potential targets of Shentong Zhuyu Decoction against LDH，and 69 key targets were screened out.The key targets were involved in the GO terms and KEGG pathways of cancer pathway，mitogen-activated protein kinase(MAPK) signaling pathway，phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) signaling pathway，tumor necrosis factor(TNF) signaling pathway，and NF-κB signaling pathway.The experimental results showed that Shentong Zhuyu Decoction could reduce the apoptosis of nucleus pulposus cells and the protein expression of NF-κB p65，MMP-13，and Caspase3(P<0.05).Conclusion:Shentong Zhuyu Decoction exerts therapeutic effect on LDH through multiple components，multiple targets and multiple pathways.The mechanism is related to the inhibition of NF-κB signaling pathway and the catabolism of extracellular matrix.