Acute kidney injury (AKI) is a potentially life-threatening condition. The injury involves the generation of inflammatory mediators which contribute to the recruitment of leukocytes to the site of inflammation. As those inflammatory mediators are secreted directly into the urine, their detection in urine could serve as potential biomarkers for the diagnosis of early kidney injury. This is a prospective cross-sectional descriptive study. Urinary samples were collected from 170 subjects who were admitted to intensive care unit (ICU) at Alkafeel Super Speciality Hospital from September 2017 to June 2018. They were tested for urinary interleukin-18 (IL-18). Among 98 patients, 20 were excluded depending on exclusion criteria. Seventy-two cases in the control group were included. The urine samples were collected at 24, 48, and 72 h after admission to ICU. AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The incidence rate of AKI among 78 patients who were admitted to ICU was 38.46%. Most of the patients with AKI belonged to stage 1 (80%) based on KDIGO guidelines2012. Urinary IL-18 levels were significantly higher (P <0.0001) in the AKI group in comparison with the non-AKI group. The result of receiver operating characteristic analysis showed that the higher area under the curve for urinary IL-18 was 0.946 measured at 24 h before development of AKI (P <0.000), with 87.5% sensitivity and 94.4% specificity. In addition, there was no significant difference of urinary IL-18 levels between the different causes of AKI. The results of the study indicate that urinary IL-18 has an excellent performance in predicting AKI in ICU patients.