To explore the mechanism of Yupingfeng Powder in the treatment of hepatocellular carcinoma(HCC).Methods:Traditional Chinese Medicines Systems Pharmacology(TCMSP) was used to retrieve the drugs in Yupingfeng Powder，and the target genes corresponding to the active components of Yupingfeng Powder were obtained.GeneCards database was used to screen out the corresponding genes of HCC，and Cytoscape 3.7.2 was used to draw the “drug-disease-component-target” network.The obtained data were imported by the SRTING database，and the protein-protein interaction(PPI) network for the core targets of Yupingfeng Powder in the treatment of HCC was constructed.The obtained data were imported into Cytoscape 3.7.2 for network topology parameter analysis and screened out based on the Degree value higher than the average value.The information on core targets of Yupinggfeng Powder in the treatment of HCC was eventually obtained，and the core targets were imported into the DAVID database to conduct Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses.Results:Ninty-two targets corresponding to the active components of Yupingfeng Powder were obtained，including cellular tumor antigen p53，B-cell lymphoma-2(Bcl-2)，vascular endothelial growth factor 2(VEGF2)，interleukin-6(IL-6)，and so on.Twenty-six core targets were screened out in the treatment of HCC，including IL-6，tumor protein p53(TP53)，tumor necrosis factor(TNF)，nitric oxide synthase 3(NOS3)，estrogen receptor 1(ESR1)，JUN，prostaglandin-endoperoxide synthase 2(PTGS2)，and so on.Conclusion:The main targets of Yupingfeng Powder in the treatment of HCC are related to the nucleus，the positive regulation of RNA polymerase Ⅱ promoter transcription and mitogen-activated protein kinase(MAPK) cascade reaction，and the activity of the steroid hormone receptor.