To predict the potential active components of Xihuang Pills against gastric cancer with blood stasis syndrome based on Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP V2.0) and to explore the molecular mechanism.Methods:The chemical constituents of Xihuang Pills were retrieved from TCMIP V2.0 and a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM), and the candidate targets of Xihuang Pills were predicted.Genes related to the gastric cancer and blood stasis syndrome were screened out and the disease-syndrome-prescription network was constructed.The core network was determined based on the network topology eigenvalue and David 6.8 was employed for the Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the core network.According to the number and frequency of the chemical components, the potential core components of Xihuang Pills against gastric cancer with the blood stasis syndrome and the corresponding targets and pathways were determined.Cytoscape 3.8.0 was used to plot the “core component-core target-core pathway” network, and Autodock 4.2 was applied for the docking of major components and core targets.Results:Xihuang Pills exerts therapeutic effect on gastric cancer with blood stasis syndrome through 4 medicinals, 13 core chemical components, 19 core targets, and 33 core pathways.The main medicinals were Moschus and Olibanum, and the pathways involved mainly included tumor pathway, carcinogenesis-related pathway, immune system pathway, and endocrine and metabolism-related pathway.Phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit gamma (PIK3CG), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), nuclear factor kappa B subunit 1 (NFKB1), tumor protein p53 (TP53), and cell division cycle 42 (CDC42) may play an important role in the treatment of blood stasis syndrome of gastric cancer.Molecular docking showed high binding affinity between the core components and the targets.In vitro experiments showed that Xihuang pills significantly inhibited the formation of mimicry channels in gastric cancer (MGC-803) cells (P<0.01), and the inhibitory effect was equivalent to 2-methoxy-estradiol (2-ME), an inhibitor of Hypoxia Inducible Faction-1 (HIF-1α).In vivo experiments showed that both Xihuang Pills and 2-ME could significantly reduce the number of mimicry channels in mouse gastric cancer tissue, and their effects were similar.Conclusion:The potential chemical components of Xihuang pills can treat the patients with blood stasis syndrome of gastric cancer and inhibit the formation of angiogenic mimicry in mice with gastric cancer.