Abstract Background Qingying decoction (QYD) is a traditional prescription in China that has been shown to be effective in treating psoriasis. However, its mechanism of action remains to be elucidated. Methods The active ingredients and targets of QYD were obtained from TCMSP database, HERB database and SwissTargetPrediction database, respectively. Differential expression gene (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were used to identify key genes associated with psoriasis. Protein-protein interaction (PPI) network was constructed using STRING platform. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DAVID database and the clusterProfiler package of R software. Cytoscape 3.9.0 software was used to screen the key components of QYD and the hub targets. Molecular docking was used to detect the binding ability between key components and hub targets. An in vitro model of psoriasis was established by stimulating keratinocyte HaCaT with a mixture of five pro-inflammatory cytokines (IL-17 A, IL-22, IL-1α, oncostatin M, and TNF-α) (M5). Cell viability and cell cycle were measured using cell counting Kit 8 (CCK-8) and flow cytometry, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect mRNA levels of hub genes, high-proliferation marker keratin 6 (KRT6) and inflammatory factors IL-1β, IL-6 and TNF-α. Protein expression levels of PI3K/AKT/FoxO pathway related targets were detected by Western blot. Results A total of 139 active ingredients of QYD were screened in this study, with 1033 targets, 59 of which overlapped with psoriasis-related genes. Quercetin, luteolin, kaempferol, beta-sitosterol and methylophiopogonanone A were considered to be the key ingredients of QYD in the treatment of psoriasis. CDC25A, TOP2A, NEK2 and CCNA2 were identified to be the hub targets. QYD could probably regulate cell cycle, T cell receptor signaling pathway and metabolic pathway to treat psoriasis. The key components of QYD had good binding affinity with hub target proteins. QYD significantly attenuated M5-induced hyperproliferation and cell cycle progression of HaCaT cells. M5 stimulation significantly upregulates the mRNA levels of CDC25A, TOP2A, NEK2, CCNA2, IL-1β, IL-6 and TNF-α, while QYD treatment reversed this effect. In addition, QYD treatment inhibited the phosphorylation of PI3K and AKT in M5-stimulated HaCaT cells and upregulated p-FOXO1 protein expression level. Conclusion QYD can inhibit the excessive proliferation and inflammatory response of keratinocytes by regulating the PI3K/AKT/FoxO pathway, suggesting that QYD may be an attractive prescription for psoriasis.