[Objectives] To collect the main active components and targets of baicalein, and to explore the relationship between their targets and COVID-19 and the treatment mechanism of potential unknown targets. [Methods] The 2 D and 3 D structures of baicalein(CAS: 491-67-8) were obtained by searching Pubchem. The predicted target of baicalein was obtained through the Pharmapper website, and the species specific target was obtained by SEA search server. The COVID-19 related genes were obtained in Genecards and OMIM. The Draw Venny Diagram online program was used to establish the visualized network map of "drug-disease-target" with baicalein monomer target and disease common target and Cytoscape(3.7.2) software. The COVID-19 gene was constructed by using Cytoscape plug-in Bisogenet, and protein-protein interaction(PPI) network was constructed by using the baicalein COVID-19 gene. The CytoNCA topology was used to analyze the network topology and construct the core network. The core network genes were analyzed by GO and KEGG. [Results] Through screening, a total of 358 effective target genes of baicalein, 23 common targets of baicalein-COVID-19, and 80 genes of PPI core network were obtained. The total of 1 648 GO biological processes including DNA metabolism, positive regulation, intracellular receptor signaling pathway, transforming growth factor β receptor signaling pathway, regulation of apoptotic signaling pathway, RNA polymerase II transcription factor binding, and 115 KEGG-related signaling pathways involving cell cycle pathways, viral oncogenic pathways, Hepatitis B pathway, Hepatitis C pathway, PI3 K-Akt pathway, and ubiquitin-mediated proteolysis, etc. [Conclusions] The effect of baicalein on COVID-19 reflects the characteristics of multiple targets, and it can also regulate the occurrence and development of COVID-19 through various channels. This study is expected to provide a certain basis for subsequent experiments.