Objective: To study the mechanism of Liuwei Dihuang Pill (LWDP) in the treatment of hypothyroidism from the perspective of network pharmacology. Methods: The active ingredients of Liuwei Dihuang pill were screened by TCMSP platform database and the target prediction was carried out. GeneCards database was used to screen genes associated with hypothyroidism.The target of Liuwei Dihuang pill in treating hypothyroidism was obtained by Venny platform. The protein-protein interaction (PPI) network, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of these targets were performed to reveal the possible mechanism of Liuwei Dihuang pill in treating hypothyroidism. Results: A total of 28 active components and 189 targets were identified from Liuwei Dihuang Pills, and 4502 targets were identified from GeneCard database. The PPI network contains 124 nodes and 323 edges. 662 biological processes (BP), 72 cell components (CC) and 127 molecular functions (MF) were obtained by GO enrichment. A total of 149 signaling pathways were obtained by KEGG enrichment analysis, and the top 20 signaling pathways were visualized and analyzed.The signal pathways related to hypothyroidism include AGE-RAGE signal pathway, lipid and atherosclerosis signal pathway, HIF-1 signal pathway, PI3K-Akt signal pathway and MAPK signal pathway. Conclusion: The main components of Liuwei Dihuang pill in treating hypothyroidism are quercetin, kaempferol, β-sitosterol, diosgenin, kadsurenone, hederagenin, sitosterol and stigmasterol. The main targets of Liuwei Dihuang pill are MAPK1, TP53, TNF, AKT1 and EGFR, and they play a therapeutic role through AGE-RAGE, lipid and atherosclerosis, HIF-1, PI 3K-Akt and MAPK signal pathways.