Abstract：Objective：To explore the molecular mechanism of Platycodonis Radix in treating non-small cell lung cancer (NSCLC) based on network pharmacology and molecular docking. Methods：The chemical components of Platycodonis Radix were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The active component targets of Platycodonis Radix were screened through Pharmmapper and Swiss Target Prediction databases. The disease targets associated with NSCLC were obtained from TTD and DrugBank databases. Protein-protein interaction (PPI) analysis was performed based on STRING Database，and PPI network was constructed via Cytoscape3.9.1 Software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of Platycodonis Radix for NSCLC were performed based on DAVID Database. The "componentstargets- signals" pathway network was constructed by CytoScape 3.9.1 Software，and the binding ability of active components of Platycodonis Radix and core targets was verified by molecular docking. The relative expression levels of core target genes were verified by qPCR in vitro. Results：A total of 7 potential active components of Platycodonis Radix were screened and 35 targets of Platycodonis Radix for NSCLC were obtained. Through the PPI network analysis and according to the Degree value， 6 core targets were obtained. After GO enrichment analysis， 94 items related to biological processes， 26 items related to molecular functions，and 47 items related to cell components were obtained. According to KEGG pathway enrichment analysis， 42 pathways such as pathway in cancer and epidermidine growth factor receptor (EGFR) tyrosine kinase inhibitor resistance in cancer were obtained. The results of molecular docking showed that there were good docking activities between taxolasin and prostaglandin G/H synthase 2 (PTGS2)， luteolin with P- glycoprotein (ABCB1) and PTGS2， robinin and EGFR. Twenty- four hours after administration，compared with that in the blank control group，the activity of A549 cells in the low- dose Platycodonis Radix extract group was decreased (P＜0.05)，and the activity of A549 cells in the high-dose Platycodonis Radix extract group was lower than that in the low-dose Platycodonis Radix extract group (P＜ 0.05). The results of qPCR showed that compared with that in the blank control group， the mRNA expressions of ABCB1，EGFR and PTGS2 of A549 cells in the low-dose Platycodonis Radix extract group were decreased (P＜0.05)，and that the mRNA expressions of ABCB1，EGFR and PTGS2 of A549 cells in the high-dose Radix Platycodonis extract group were lower than those in the low-dose Platycodonis Radix extract group (P＜0.05). Conclusion： Multiple active components of Platycodonis Radix may inhibit the expressions of ABCB1，EGFR and PTGS2，and then regulate pathway in cancer and EGFR tyrosine kinase inhibitor resistance to treat NSCLC. Platycodonis Radix extract may improve NSCLC in a dose- dependent manner.