Aim To explore the key genes in the blood transcriptome of atherosclerosis patients based on blood transcriptomics.Methods Three datasets GSE12288,GSE27034 and GSE90074 were extracted from the GEO data-base and performed the merging and normalization processing.The differential genes in peripheral blood samples of ather-osclerosis patients and controls were analyzed,and enrichment analysis of differentially expressed genes were performed.Then weighted gene co-expression network analysis was performed for all genes.Using differentially expressed genes to construct protein-protein interaction(PPI)network,and using CytoHubba to screen key genes based on co-expression net-work and PPI network.And the expression levels of key genes were detected by RT-qPCR.Results 74 down-regu-lated genes and 145 up-regulated genes were identified between atherosclerosis patients and controls.GO and KEGG en-richment analyses revealed that they were significantly enriched in neutrophil activation,granulocyte activation,cytokine-cytokine receptor interaction and chemokine signaling pathway.In addition,the top 10 genes in the co-expression network and the top 20 genes in the PPI network were also identified,in which PRF1,NKG7,GZMB and CCL5 played a high core role in the PPI network and co-expression network.The RT-qPCR results showed that compared with the non coronary atherosclerosis controls,the mRNA expression levels of PRF1 and GZMB in peripheral venous blood peripheral blood mono-nuclear cell(PBMC)of coronary atherosclerosis patients were significantly reduced(P＜0.05),while the mRNA expres-sion levels of NKG7 and CCL5 were significantly increased(P＜0.05).Conclusion PRF1,GZMB,NKG7 and CCL5 may be key genes in the blood transcriptome of atherosclerosis patients,and are expected to be potential biomarkers for diagnosis and treatment of atherosclerosis.