<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Quality of life (<jats:styled-content style="fixed-case">QOL</jats:styled-content>) as a treatment outcome has not yet been evaluated among patients receiving a specific treatment regimen by treatment phase in a consistent manner. This exploratory cross‐sectional study evaluated the <jats:styled-content style="fixed-case">QOL</jats:styled-content> of children with acute lymphoblastic leukemia (<jats:styled-content style="fixed-case">ALL</jats:styled-content>) receiving one of the most popular treatment regimens in Japan (Japan Association of Childhood Leukemia Study <jats:styled-content style="fixed-case">ALL</jats:styled-content>‐02 revised protocol).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Children aged 5–18 years with newly diagnosed B‐cell precursor <jats:styled-content style="fixed-case">ALL</jats:styled-content> were included. The Pediatric Quality of Life Inventory<jats:sup>™</jats:sup> 4.0 Generic Core Scales (Peds<jats:styled-content style="fixed-case">QL</jats:styled-content>‐J) were completed by children with <jats:styled-content style="fixed-case">ALL</jats:styled-content> and their siblings, as well as by age‐ and sex‐matched healthy controls. Peds<jats:styled-content style="fixed-case">QL</jats:styled-content> Cancer Module (Peds<jats:styled-content style="fixed-case">QL</jats:styled-content>‐C) scores were also collected from children with <jats:styled-content style="fixed-case">ALL</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:styled-content style="fixed-case">QOL</jats:styled-content> in children with <jats:styled-content style="fixed-case">ALL</jats:styled-content> of the consolidation phase group was significantly decreased compared with that of healthy controls, except in the area of emotional functioning. Regarding the maintenance phase group, <jats:styled-content style="fixed-case">QOL</jats:styled-content> impairment was noted in the physical and school functioning, but no differences were noted in social functioning. The off‐treatment group had a large effect size only for physical functioning, and the social functioning score was even better in children with <jats:styled-content style="fixed-case">ALL</jats:styled-content> than in matched controls. <jats:styled-content style="fixed-case">QOL</jats:styled-content> of children with <jats:styled-content style="fixed-case">ALL</jats:styled-content> differed with treatment phase. Effect size varied with function and treatment phase.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p><jats:styled-content style="fixed-case">QOL</jats:styled-content> may change with the progression of treatment, and the timing of these changes varied according to function and problem.</jats:p></jats:sec>