Introduction: In the South African public health system, children with cancer are admitted to specialised oncology units for the duration of their treatment. These units therefore become the children's temporary living environment for varying periods of time, which may disrupt their participation in daily activities and consequently their health-related quality of life (HRQoL). Aim: The purpose of the study was to determine the HRQoL of children admitted with cancer from both their own and their parents' perspective. Methodology: A quantitative, descriptive, cross-sectional study was conducted at a tertiary hospital in Gauteng with a specialist oncology unit. Structured interviews were conducted with the children aged 8-12 years using the PedsQL TM Generic Core Scale (4.0) and Cancer Module (3.0). The parent's perspective was explored using the Parents proxy forms of both instruments. Results: Twenty-five children and their parents participated in the study. Most children in the sample were males with Leukaemia. All children and parents reported the children's functioning at an intermediate level which suggests that these children may be at risk for HRQoL deficits. Children's HRQoL was impacted by psychosocial functioning and change in schooling on the PedsQL TM Generic Core Scale (4.0), while parents felt physical functioning played a greater role in determining the child's HRQoL. On the PedsQL TM Cancer Module (3.0) both the children and parents felt that 'procedural anxiety' had an effect, although from the parents' perspective, 'worry' accounted for the greatest deficits in their children's HRQoL. Conclusion:This study indicates that occupational disruption is experienced by children during the long-term treatment of cancer. It is suggested that occupational therapists use available instruments to monitor and provide support for the effect of an impaired HRQoL.