To explore the mechanism of Huangqi(Astragali Radix)-Danshen(Salviae Miltiorrhizae Radix et Rhizoma) in the treatment of liver cancer based on network pharmacology and verify the related pathways by in vitro experiments.Methods:The active ingredients of Huangqi and Danshen and related protein target names were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and related literature.Unitprot database was used to correct the gene names of the protein targets，and Cytoscape3.8.0 software was used to plot the drug-component-target network diagram.The gene targets of liver cancer were collected through the Drugbank，Online Mendelian Inheritance in Man(OMIM)，Therapeutic Target Database(TTD)，and GeneCard，and intersected with gene targets of Huangqi-Danshen to obtain the common targets.Core targets were subjected to protein-protein interaction(PPI) analysis，Gene Ontology(GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses using String 11.0 database and Metascape database，respectively.Finally，the efficacy of the drugs on liver cancer cells was detected by CCK-8 assay and flow cytometry assay，and the expression levels of PI3K and AKT genes were detected by PCR assay.Results:Seventy-six active ingredients and 118 core targets of Huangqi and Danshen were screened out.After PPI analysis，Huangqi and Danshen in the treatment of liver cancer might be related to targets，such as AKT1，JUN，MAPK1，MAPK8，IL6，MAPK14，FOS，ESR1，EGFR，and CCND1.GO and KEGG enrichment analyses showed that Huangqi and Danshen mainly acted on transcription factors，participated in the process of apoptosis，and acted through cancer-related pathways，PI3K-AKT pathway，and TNF signaling pathway.CCK-8 assay，flow cytometry assay，and PCR assay showed that Huangqi and Danshen were effective in the treatment of liver cancer and exerted an apoptotic effect through the P13K-AKT signaling pathway.Conclusion:Huangqi-Danshen herbal pair has the characteristics of a multi-component，multi-target，and multi-pathway synergistic effect in the treatment of liver cancer，where the PI3K-AKT signaling pathway plays an important role.