In summary, a comprehensive bioinformatics analysis of two IRI-AKI models was conducted, and it was found that several hub genes, such as Jun, Stat3, Myc, Cdkn1a, Hif1a, Fos, Atf3, Mdm2, Egr1, and Ddit3, as well as the MAPK, PI3K-Akt, and TNF signaling pathways, may play a pivotal role in the physiological and pathological processes of IRI-AKI. This evidence concerns the gene TNF and acute kidney injury.