Introduction: The aim of the study was to determine the health related quality of life (HRQoL) and family functioning of parents whose children were receiving active phase cancer treatment during a hospital admission. Methodology: A quantitative, descriptive, cross-sectional study was conducted in a specialist oncology unit within a tertiary hospital in Gauteng, South Africa. Structured interviews were conducted with the parents of children with cancer, to determine their Health Related Quality of Life (HRQoL) using the PedsQLTM Family Impact Module (2.0). Results: Twenty-Five parents participated, with ages ranging from 26 to 48 years. Most were female, with high school educational level and unemployed. Parents reported intermediate or low HRQoL particularly in the physical and worry components. Parent participants reported family functioning within the intermediate level of HRQoL. The HRQoL of parent participants in this study differed from that reported by parents in another study in a low-middle income context. Conclusion: This study indicated the diagnosis and treatment of child’s cancer created challenges, which had a negative impact on parents’ HRQoL and family functioning.