The aim of this study was to investigate the effects of high-dose corticosteroids on behavior and quality of life of children with acute lymphoblastic leukemia (ALL) in maintenance therapy. Forty-three families (patient and/or parent) completed the Child Behavior Checklist (CBCL), the Pediatric Quality of Life Inventory (PedsQL) Cancer module questionnaires, a checklist of common complaints, and a descriptive intervention data questionnaire, on and off steroids, each child serving as his/her own control. Children 5 years and younger had higher CBCL scores in the somatic complaints, affective problems, internalizing, externalizing, and total problem scales, when comparing “on-steroid” to “off-steroid” periods (P<0.01). Children 6 years and above had higher CBCL scores in the externalizing, aggressive, and oppositional defiant problem scales on steroids compared with off steroids (P<0.05). Older children had larger changes on dexamethasone, compared with prednisone (P<0.05). On the PedsQL questionnaire, parents reported more pain and hurt (P<0.001), nausea (P=0.042), and procedural anxiety (P=0.013) when children were on steroids compared with off steroids. Corticosteroid treatment during ALL maintenance therapy is associated with behavior and emotional disturbances and adversely affects quality of life. Dexamethasone is associated with more significant behavioral changes in older children.