Background: Tumor lysis syndrome (TLS) is a major metabolic complication in patients with malignancy after initiation of chemotherapy or spontaneously without treatment. The role of Rasburicase (a recombinant urate-oxidase enzyme) in prevention and treatment of TLS has been demonstrated in recent years. We aimed to investigate the efficacy of a single dose of rasburicase in reducing the risk of TLS in children at high risk.Methods: we conducted a retrospective analysis of 560 children with various malignancies in a single referral center. On the basis of the reference values previously established in our center hyperuricemia and TLS were defined. Tumor lysis syndrome development was the primary outcome.48 children with a mean age of 7.1 years (range: 3 months to 15.8 years) developed tumor lysis syndrome.The most common malignancies were B-precursor acute lymphoblastic leukemia (ALL) (45%) followed by non-Hodgkin lymphoma (NHL) and Wilms’ tumor (each 10.4%), respectively. They received normal saline intravenously at a rate of 4-5 L/m2/day in 24-48 hours prior to initiating chemotherapy. Plasma samples were drawn to detect uric acid, calcium, phosphate, potassium, creatinine and blood urea nitrogen (BUN) 4 hours before administering a single dose of IV rasburicase (0.2 mg/kg over 30 minute). Laboratory markers were evaluated again 4 and 24 hours after administering rasburicase.Results: All patients with diagnosis of TLS had significantly decreased uric acid levels following single dose of rasburicase except 1 patient (2.1%) (P<0.001). Mean plasma uric acid concentration before treatment was 10.0±4.2 mg/dL and 4 hours after treatment declined to 2.2±5.5 (P<0.001). Hyperphosphatemia was also detected in 43.7% of these 48 cases which significantly decreased to 16.7% (P=0.012). Plasma uric acid levels remained low one day after treatment. No side effects were detected.Conclusion: Rasburicase is a safe and highly effective drug in children with hyperuricemia in the setting of malignancy at risk of developing TLS.