Hyperuricemia can cause renal damage and acute kidney injury or be secondary to renal failure and reduced excretion. Rasburicase, a recombinant urate oxidase, is a common treatment for hyperuricemia from different etiologies. There are scarce reports on rasburicase treatment for neonatal Acute Kidney Injury (AKI) with hyperuricemia to prevent renal damage secondary to hyperuricemia. Herein we report a case of neonatal AKI with hyperuricemia that was treated with a single dose of rasburicase. Serum uric acid declined immediately after rasburicase infusion and remained in the normal range since then. In contrast to previous reports, the normalization of uric acid levels was not accompanied by recovery from AKI and serum creatinine levels remained elevated for a long period. The neonate recovered from AKI only 2 weeks post rasburicase treatment. This case report highlights the importance of uric acid levels in neonatal AKI and suggests treatment with rasburicase in cases of hyperuricemia and acute kidney injury in neonates.