ABSTRACT: BACKGROUND: Most studies on Health-related Quality of Life (HRQOL) in children with cancer were conducted in developed countries. The aims of this study were to assess the HRQOL in childhood acute lymphoblastic leukemia (ALL) patients in Indonesia and to assess the influence of demographic and medical characteristics on HRQOL. METHODS: After cultural linguistic validation, a cross-sectional study of HRQOL was conducted with childhood ALL patients and their guardians in various phases of treatment using the Pediatric Quality of Life InventoryTM (PedsQLTM) 4.0 Generic Core Scale and the Pediatric Quality of Life InventoryTM (PedsQLTM) 3.0 Cancer Module. RESULTS: Ninety-eight guardians and 55 patients participated. The internal consistency of both scales ranged from 0.57 to 0.92. HRQOL of Indonesian patients was comparable with those in developed countries. There were moderate to good correlations between self-reports and proxy-reports, however guardians tended to report worse HRQOL than patients. Children of the 2-5 year-group significantly had more problems in procedural anxiety, treatment anxiety and communication subscales than in older groups (p<0.05). In the non-intensive phase HRQOL was significantly better than in the intensive phase, both in patient self-reports and proxy-reports. CONCLUSION: Younger children had more problems in procedural anxiety, treatment anxiety and communication subscales. Therefore, special care during intervention procedures is needed to promote their normal development. Psychosocial support should be provided to children and their parents to facilitate their coping with disease and its treatment.