Objective:To analyze the mechanism of Kaixin Powder in intervening post-stroke cognitive impairment (PSCI) through network pharmacology and proteomics analysis.Methods:TCMSP, ETCM, TCMID, and BATMAN databases were used to retrieved the active components and gene targets of Kaixin Powder. Differential genes in PSCI patients' blood samples were determined using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). A protein-protein interaction network (PPI) was constructed using the STRING database, and a drug-PSCI-gene network was built with Cytoscape software. GO and KEGG enrichment analysis of targets were performed using the DAVID database, and the effective components were docked with targets using AutoDock software for molecular docking verification.Results:A total of 2 292 drug targets within Kaixin Powder were identified, with 248 differential genes found in clinical samples from PSCI patients, including 125 up-regulated and 123 down-regulated genes. KEGG enrichment analysis identified pathways including the TNF signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and MAPK signaling pathway. The molecular docking results indicated that the three active components of Kaixin Powder, β-sitosterol, riboflavin, and musk ketone, had strong binding effects with four target proteins CXCR4, APOE, AGT, and SLC2A1.Conclusion:The active components of Kaixin Powder, such as β-sitosterol, riboflavin, and musk ketone, may treat PSCI by modulating the targets such as CXCR4, APOE, AGT, and SLC2A1, thereby activating or inhibiting pathways such as TNF signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and MAPK signaling pathway.