Objective To explore the possible preventive mechanism of Hunan expert group recommended Chinese medicine prescription of No. 2 (Pre-No. 2) against coronavirus disease 2019 (COVID-19) by network pharmacology method. Methods The target proteins of effective components and active compounds in Pre-No. 2 were screened by searching the Tradi-tional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). A component-target-disease interac-tion network of Pre-No. 2 was constructed by Cytoscape 3.7.2, gene ontology (GO) analysis, and Kyoto encyclopedia of genes and genomes (KEGG) analysis of target protein pathway by DAVID. Results A total of 163 compounds and 278 target protein targets in Pre-No. 2 were collected from the TCMSP database. Kaempferol, wogonin, 7-methoxy-2-methyl isoflavone, formononetin, isorhamnetin, and licochalcone A were the most frequent targets in the regulatory network. GO enrichment analysis showed that Pre-No. 2 regulated response to virus, viral processes, humoral immune responses, defense responses to virus and viral entry into host cells. KEGG enrichment analysis showed that the formula regulated the NF- κ B signaling pathway, B cell receptor signaling pathway, viral carcinogenesis, T cell signaling pathway and Fc γ R-mediated phagocytosis signaling pathway. Conclusions Pre-No. 2 may play a preventive role against COVID-19 through regulation of the Toll-like signaling, T cell signaling, B cell signaling and other signaling pathways. It may re-gulate the immune system to protect against anti-influenza virus.