To explore the mechanism of Shashen Maidong Decoction(SMD) against lung cancer based on network pharmacology and molecular docking.Methods:Chemical components and targets of SMD were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN-TCM)，and targets related to lung cancer from Online Mendelian Inheritance in Man(OMIM)，DrugBank，and GeneCards.Cytoscape 3.8.0 was employed to construct the “medicinal-active component-key target-disease-signaling pathway” network，and STRING to generate the protein-protein interaction(PPI) network.Cytoscape was applied for cluster analysis of proteins，and Metascape for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment，which were visualized by R language.Finally，molecular docking of core components with proteins was performed.Results:A total of 192 active components and 3 585 targets of SMD and 1 910 lung cancer-related targets were screened out.The disease and the decoction shared 191 targets.CytoNCA showed that the core targets were JUN，mitogen-activated protein kinase(MAPK) 8，Myc proto-oncogene protein(MYC)，MAPK14，signal transducer and activator of transcription 3(STAT3)，MAPK1，REL-associated protein(RELA)，tumor protein 53(TP53)，and interleukin-6(IL-6).The targets were involved in the GO terms of 2 684 biological processes，117 cellular components，and 210 molecular functions，and the pathways of cancer pathway，tumor necrosis factor(TNF) signaling pathway，the role of proteoglycans in cancer，microRNAs in cancer tissues，platinum resistance，and tumor transcriptional regulation disorder.Molecular docking indicated that the main components quercetin，stigmasterol，β-carotene，kaempferol，β-sitosterol，and naringenin had high binding affinity to the core proteins STAT3，MAPK14，TP53，TNF，IL-6，and MYC.Conclusion:SMD may act on targets such as STAT3，MAPK14，and TP53 to intervene in the progression of lung cancer through signaling pathways such as cancer pathway，platinum resistance and tumor transcriptional regulation disorder.