Objective We analyzed the mechanism of action of glabrous greenbrier rhizome in the treatment of fever based on network pharmacology. Methods We screened for the active components and targets of Poria cocos using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform( TCMSP, https: / / tcmspw. com/ tcmsp.php), with Oral bioavailability(OB) and Drug-likeness(DL) as indicators. We used the UniProt database to convert discovered entries to respective gene symbols, and then GeneCards to obtain disease-related information that intersects with glabrous greenbrier rhizome target genes. We then constructed a protein interaction network using the STRING (Search Tool for the Retrieval of Interacting Genes/ Proteins) Web resource and R software for Gene Ontology ( GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis. AutoDock Vina software was used for molecular docking modeling simulations. Results Twelve active ingredients of Poria cocos, corresponding to 145 gene symbols were discovered in our analyses. Of these, five are core components of glabrous greenbrier rhizome and another five are fever core targets. glabrous greenbrier rhizome may affect regulation of the body’ s response to external stimuli and resistance to EGFR inhibitors.Molecular docking simulations show a strong affinity for the core components and core targets. Conclusions Naringenin, β-sitosterol, quercetin, diosgenin, and stigmasterol are the primary core components of glabrous greenbrier rhizome treatment, and the main targets are IL-6, EGFR, CASP3, MYC, and VEGFA.