To explore the molecular mechanism of Xiaoyao Powder in the treatment of post-stroke depression(PSD) based on network pharmacology and molecular docking.Methods:The main active components and targets of Xiaoyao Powder were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)，Swiss Target Prediction，and PharmMapper.The disease targets were obtained from the DrugBank，GeneCards，and Online Mendelian Inheritance in Man(OMIM).Then the component-disease intersection targets were obtained.STRING database was used for protein-protein interaction(PPI) analysis，and Cytoscape software was used to screen the core targets and core components.Metascape platform was used for Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses，and Autodock Vina platform was used for molecular docking.Results:The core components of Xiaoyao Powder included kaempferol，naringenin，isorhamnetin，14-acetyl-12-senecioyl-2E，8E，10E-atractyltriol，and quercetin.The core targets included tumor necrosis factor(TNF)，albumin(ALB)，protein kinase B(AKT1)，tumor suppressor gene 53(TP53)，and vascular endothelial growth factor A(VEGFA).The main pathways involved the cancer pathway and Janus kinase(JAK)/signal transducer and activator of transcription protein(STAT) signaling pathway.Molecular docking results showed that naringenin and isorhamnetin bound to ALB most stably.Conclusion:Xiaoyao Powder has a therapeutic effect on PSD，and its mechanism may be related to the regulation of the JAK/STAT pathway through the core targets of TNF，AKT1，and ALB，thereby improving the biological processes such as inflammation and oxidative stress.