Interferon regulatory factors (IRFs) are transcription factors with a conserved N-terminal helix-loop-helix DNA-binding domain 1. IRF family plays a pivotal role in regulating interferon transcription, immune cell development, cell growth, apoptosis, and oncogenesis.2 Despite considerable research, the roles of IRFs in cancer development, metastasis, drug resistance, and prognosis remain unclear. Through multidimensional correlation analysis, we examined the association between IRFs and various cancer characteristics, including clinical and immune subtype analysis, stemness, tumor microenvironment (TME), and drug sensitivity, by utilizing The Cancer Genome Atlas (TCGA) data. Moreover, the classification and prognostic role of IRF1 were further validated through immunohistochemistry staining of kidney renal papillary cell carcinoma (KIRP) clinical tissues. This research enriches our understanding of the IRFs' roles in cancer and their clinical applications.