To explore the anti-influenza mechanisms of Flos Caryophylli(clove).Methods:The active ingredients of Flos Caryophylli were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and previous literature.SwissTargetPrediction was utilized to obtain the corresponding targets of the active ingredients of Flos Caryophylli.Influenza-related targets were searched out from GeneCards.The common targets were obtained by intersection.Cytoscape 3.7.2 was employed for the construction of “Flos Caryophylli-active ingredient-target-influenza” network.String was adopted to construct a protein interaction network(PPI) of the common targets.Gene ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed by Metascape.Autodock Vina1.1.2 was used for molecular docking to study the interactions of the active ingredients of Flos Caryophylli with key influenza proteins and influenza virus proteins,and then their action network was constructed.Results:A total of 28 ingredients,such as rhamnazin-3-O-β-D-glucopyranoside,isoquercitrin,quercetin-3-O-β-D-glucuronide,rhamnetin-3-O-β-D-glucuronide-6″-methyl,and 1,2,3,6-tetra-O-galloylglucose and 209 targets of Flos Caryophylli in treatment of influenza,such as MAPKs,TNF,AKT1,TP53,EGFR,CASP3,and HSP90AA1 were obtained in the “Flos Caryophylli-active ingredient-target-influenza” network.Immune response activation,enzyme activity regulation,apoptosis regulation,cytokine regulation,and other biological processes were mainly related to anti-influenza by Flos Caryophylli from the GO functional enrichment screening,and PI3K-AKT,MAPK,apoptosis,chemokine,influenza A and other signaling pathways were involved from the KEGG pathway analysis.The molecular docking network showed that the 28 active ingredients could dock to multiple influenza virus proteins,such as HA,NA,and M2.Conclusion:Flos Caryophylli could interact with influenza virus proteins through multiple ingredients,and act on multiple targets and regulate multiple signaling pathways,which affected inflammatory response,immune response,apoptosis and influenza virus replication,and finally achieved the effect of inhibiting influenza.