Acute kidney injury (AKI) is an independent risk factor for neonatal death. Since neonatal early renal injury usually has no specific clinical symptoms, many AKI cases are often missed the best time of early intervention if there is no relevant examination. Perinatal asphyxia (PA) can lead to AKI. The study aimed to assess efficacy of serum cystatin C (CystC) in early prediction of AKI in full-term neonates with PA. The study was conducted at the neonatal intensive care unit, Assiut University Children Hospital from January 2019 to January 2021. Seventy full-term neonates with documented PA were enrolled in the study. Baseline laboratory data and serum CystC levels were assessed. Out of those 70 neonates with PA, 21 (30%) developed AKI, while 49 (70%) neonates did not develop AKI. Majority of non-AKI group had stage-I hypoxic-ischemic encephalopathy (HIE) (61.2%), while majority of AKI had stage-III HIE (61.9%). A significantly higher serum CystC level was found among AKI group than those without AKI (1.50 0.12 vs. 0.90 0.14, p < 0.001). The predictors for AKI among neonates with PA were low birth weight, serum CystC levels, hypotension, and stage-III HIE. Serum CystC has 94.3% overall accuracy for prediction of AKI. In conclusion, AKI in neonates with PA is common. CystC is a promising biomarker in early prediction of AKI in such cases. Future studies are warranted to confirm these findings.