Objective： To explore the molecular mechanism of Sini SAN in the treatment of post-stroke depression based on network pharmacology and molecular docking techniques. Methods: Active ingredients and therapeutic targets in Sini SAN were searched through TCMSP database. Gene targets of post-stroke depression were collected using GeneCards, OMIM and PharmGkb databases. The intersection targets were selected as potential targets and imported into String database to establish protein interaction (PPI) network. Network topology analysis by Cytoscape software. PPI targets were introduced into R for gene ontology (GO) function and Kyoto Encyclopedia of Genomes (KEGG) pathway enrichment analysis. The “pathway-target” network was constructed and the key targets were screened, and the AMDock platform was used to interconnect the target with the active ingredient to screen the potential pharmacodynamic ingredient.Results: 104 kinds of drug chemical components, 235 targets and 1 001 disease target genes of Sini SAN were obtained from the database, including 7 kinds of drug core components and 77 overlapping genes with diseases. Through software analysis, MMP9, AKT1, IL-10, ESR1, IL-6, HIF1A, IL-1B, CASP3 and TNF were the core genes. GO enrichment analysis showed that it was mainly through the molecular functions of protease binding, nuclear receptor activity, cytokine activity, estrogen response element binding, etc., in the membrane raft, membrane microregion, plasma membrane raft, Bcl-2 family protein complex, plasma membrane lateral, neuron cell body, endoplasmic reticulum cavity and other action sites. The reaction to the decrease of oxygen content, the regulation of apoptosis signaling pathway, the reaction to lipopolysaccharide and other processes play a role. KEGG analysis showed AGE-RAGE signaling pathway, p53 signaling pathway, TNF signaling pathway, estrogen signaling pathway, HIF-1 signaling pathway and other major signaling pathways. Conclusion: Sini SAN may act on MMP9, IL-6, HIF1A, IL-1B, CASP3 and other potential targets through various active ingredients such as quercetin, luteolin, kaempferol, chenetin, naringin, isorhamnetin, and ononin. It mediates AGE-RAGE signaling pathway, estrogen signaling pathway, HIF-1 signaling pathway and other signaling pathways to play an effective role.