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Introduction: L-asparaginase chemotherapy often causes hepatotoxicity and affects complete remission in pediatric acute lymphoblastic leukemia (ALL). This study aims to investigate the risk factors that affect the incidence of hepatotoxicity caused by L-asparaginase chemotherapy in ALL children. Methods: An observational study with prospective sampling was conducted at Dr. Soetomo Hospital, Surabaya. The inclusion criteria included ALL children aged 1-18 years, undergoing ALL Induction phase chemotherapy based on the 2018 Indonesian Children's ALL protocol as evidenced by bone marrow aspiration, receiving L-asparaginase chemotherapy, and obtaining written consent from parents or guardians. Each child had 3 ml of blood drawn from a peripheral vein to assess their complete blood count, alanine transaminase (ALT) levels, and albumin level. Results: Thirty-two children with ALL were collected. Two of them were excluded due to allergic reaction and enable to continue the L-asparaginase chemotherapy. Thirty of them were eligible participants. Approximately 53.3% of ALL children aged ≤ seven years. Fourteen (47%) children with ALL were included in the standard-risk group and 16 (53%) of them included high-risk group. There were significant differences in ALT levels between the four stages of observation (p=<0.001). Twenty-two ALL children had hepatotoxicity (73.3%), while 8 had non-hepatotoxicity (26.7%). Two risk factors had a significant influence on the occurrence of hepatotoxicity due to L-asparaginase chemotherapy including age and hypoalbuminemia (p=0.045, p=0.028). Conclusion: Age and hypoalbuminemia were the risk factors that might affect the incidents of hepatotoxicity. Clinical monitoring before and after treatment needs to be done to prevent poor outcomes. [ABSTRACT FROM AUTHOR]