Background: acute kidney injury (AKI) is a syndrome characterized by a rapid (hours to days) deterioration of kidney functions. It is often diagnosed in the context of other acute illnesses and is particularly common in critically ill patients. The clinical consequences of AKI include the accumulation of waste products, electrolytes, and fluid, but also less obvious effects, including reduced immunity and dysfunction of non-renal organs (organ cross-talk). Aim of the Work: was to assess the role of serum Cystatin C in early prediction of Acute Kidney Injury in critically ill patients. Patients and Methods: This a prospective cohort study included a total of 30 critically ill patients who suffered of Acute Kidney Injury and 30 subjects confined to the same age as control, attending at ICU, Al-Azhar University Hospitals. Blood samples were taken for estimation of serum cystatin C and serum creatinine at (2, 24, 48 and 72 hours). Results: showed that at day zero at 2 hours all patient showed normal kidney functions, and no one has acute kidney injury after 24 hours about 10 patient developed acute kidney injury according to KDIGO classification with a percentage of 33.3%. after 48 hours all 30 patients developed acute kidney injury according to KDIGO classification with a percentage of 100% and after 72 hours the patients state began to improve and only 28 patients have acute kidney injury with a percentage of 93.3% and level of serum creatinine started to decrease to all patients. This was due to treatment and interference to the patients. Conclusion: Cystatin C level is a valuable biomarker in prediction and early detection of acute kidney injury. Moreover, cystatin C level may be also used for prognosis of cases of acute kidney injury. Further a large-scale study may be needed to validate its predictive value.