Introduction Diarrhea associated hemolytic-uremic syndrome (D+HUS) is the common etiology for acute kidney injury in children. There is still no cure for D+HUS, however careful supportive care is effective. It includes management of fluid and electrolytes, control of hypertension, red blood cell transfusions, and early institution of dialysis. Hyperuricemia during the acute phage contributes to further renal damage. We explored if aggressive management of hyperuricemia with rasburicase, a recombinant urate oxidase, may accelerated the recovery of children with D+HUS. Methods We retrospectively analyzed the medical records of pediatric D+HUS patients who were admitted to Seoul National University Children’s Hospital between 2001 and 2016. D+HUS was defined as hemolytic anemia, thrombocytopenia, acute renal impairment and preceding diarrhea. Results A total of 72 patients (M:F = 36:36) were enrolled. Their median age was 3.2 years old. Median values of the highest white blood cell, the lowest hemoglobin, the lowest platelet, and the highest uric acid were 14,650 /ul, 6.3 g/dl, 24,000 /ul, and 12.6 mg/dl. Sixty six (91.7%) had followed-up an average 1377 days (range 6-5,806). Twelve (16.7%) were treated with rasburicase. It was administered once at a median dose of 0.11 (range 0.06–0.20) mg/kg. There was no difference in age, sex, the highest white blood cell, the lowest hemoglobin, the lowest estimated glomerular filtration rate, and the highest uric acid between the group treated with rasburicase and the group without it. The lowest platelet in the group with rasburicase was lower (18,000 vs 33,000; P = 0.002). In group treated with rasburicase, hyperuricemia (≥ 7 mg/dl) was rapidly reversed (2.4 vs 6.5 days; P 0.001). Median hospital length of stay was shorter in group with rasburicase (12.9 vs 18.2 days; P = 0.043). There was no difference in dialysis status (66.6% vs 55.0 %; P = 0.536) and the duration of dialysis (5.5 vs 8.6 days; P = 0.262). There was no difference in the incidence of proteinuria among the two groups (8.3 vs 9.3 %; P = 1.000) in the last follow-up. No patients developed end stage renal disease. Conclusions Rasburicase reduces the number of hospital days for pediatric D+HUS patients. However, it does not reduce the requirement of dialysis in acute phage and event of proteinuria after long-term follow-up.