The interferon regulatory factor (IRF) family was correlated to diverse diseases. However, systematic studies of the IRF gene family in acute myeloid leukemia (AML) have not been reported yet. We analyzed the different transcripts of the IRF family associated with the survival and clinical data of patients with AML via the GEPIA, LinkedOmics, and TCGA databases. The results revealed that the expression levels of IRF1/2/4/5/7/8/9 were up-regulated while those of IRF3/6 were down-regulated in AML patients compared with normal donors. Moreover, high expression levels of IRF1/7/9 were significantly correlated with poor overall survival (OS). We further collected the clinical and survival data of newly diagnosed AML patients from the First Affiliated Hospital of Xiamen University from April 2018 to September 2020. In consistent with the outcomes from bioinformatics, the results from analysis of the biospecimens in our center showed that high expression levels of IRF1 and IRF7 predicted a poor prognosis. Overall, our study highlighted that the overexpression of IRF1/7/9 may be related with adverse prognosis and dismal survival in AML patients, indicating that the IRF family might serve as potential therapeutic targets.