Ursodeoxycholic acid (UDCA) possesses a hepatoprotective effect in drug-induced hepatotoxicity. In a prospective randomized parallel study, 39 children with acute lymphoblastic leukemia (ALL) were randomized to receive UDCA with chemotherapy for 6 months, then discontinued UDCA and were followed up for 3 months, (UDCA group) (N = 19) or receive chemotherapy without UDCA and followed up for 9 months (control group) (N = 20). In this pilot study, UDCA treatment was associated with a trend toward decreased levels of hepatic transaminases when concomitantly administered with chemotherapy and, therefore, safer outcome in children with ALL. Future studies with a larger sample size are needed to confirm the efficacy and safety of UDCA in this setting.