To identify biomarkers associated with CD8+ T cells in coronary artery disease (CAD) and initially explore their potential role in the tumor immune microenvironment.CAD-related datasets GSE12288, GSE34198, and GSE66360, were downloaded from the GEO database. First, GSVA was performed based on the GSE12288 dataset. Then WGCNA analysis was performed to identify the most relevant module and candidate hub gene for CD8+ T cells, followed by GO and KEGG analysis of this module. Secondly, the relationship between candidate hub genes and CD8+ T cells was verified using GSE34198 and GSE66360, which led to the identification of hub genes. The relationship of hub genes with CD8+ T cells in cancer was analyzed using the TIMER database. Methylation analysis of hub genes was performed using the DiseaseMeth database. CAD, pan-cancer, pan-cell lines, and pan-normal tissues, correlations between hub genes. In addition, potential drugs and TFs associated with hub genes were predicted, and the ceRNA network was constructed. Finally, GSEA was performed separately for hub genes.CAD was shown to be associated with immune response by GSVA analysis. WGCNA identified the blue module as most related to CD8+ T cells and identified nine candidate hub genes. The relevance of CAD to immunity was further confirmed by GO and KEGG analysis of the module. Two additional datasets validated and identified three hub genes (FBXO7, RAD23A, and MKRN1) that significantly correlated with CD8+ T cells. In addition, we found that hub genes were positively associated with CD8+ T cells in TGCT, THCA, and KICH cancers by our analysis. Moreover, the hub gene was differentially methylated. We also analyzed the correlation between hub genes in CAD, different cancers, different cell lines, and different normal tissues. The results of all the analyses showed a positive correlation between them. Finally, we successfully constructed hub gene-associated TF-gene and ceRNA networks and predicted 11 drugs associated with hub genes. GSEA suggests that hub genes are related to multiple immune response processes.FBXO7, RAD23A, and MKRN1 are significantly associated with CD8+ T cells in CAD and multiple cancers and may act through immune responses in CAD and cancer.Copyright © 2022 Zhao, Wu, Wei, Xu and Zheng.