Objective  To explore the significance of macrophage migration inhibitory factor (MIF) in the early diagnosis and prognostic assessment of acute kidney injury (AKI) due to sepsis. Methods  A total of 121 patients with sepsis admitted to our hospital from July 2017 to May 2023 were retrospectively selected. The serum MIF levels at the time of admission to the intensive care unit were detected by enzyme-linked immunosorbent assay. Patient’s clinical and laboratory measurements and 28day mortality data were collected. Parameters in both the AKI and non-AKI groups were compared, and the ability of MIF to identify septic patients with or without comorbid AKI and with or without death within 28 days was clarified by the receiver-operating characteristics (ROC) curve. Results  Seventy-three (60.33%) of the included patients had combined AKI. MIF levels were significantly higher in patients in the AKI group than that in the non-AKI group [(6.82±1.58)ng/ml vs. (4.83±1.19)ng/ml, t=7.883, P＜0.001], and in the 28-day mortality group than those who survived 28 days [(7.33±1.74)ng/ml vs. (5.62±1.52)ng/ml, t=5.092, P＜0.001]. The results of multivariate binary logistic regression showed that MIF level (OR=3.240, 95% CI:1.114～11.549, P=0.023) was an independent risk factor for comorbid AKI in patients with sepsis. The area under the curve for MIF to identify AKI occurrence and 28day mortality in patients with sepsis were 0.85 and 0.80, respectively.  Conclusion    Elevated MIF level is a risk factor for comorbid AKI and poor short-term prognosis in patients with sepsis, which warrants clinical attention.