Background: Children with cancer often experience decreased quality of life (QOL) throughout the illness trajectory. The purpose of this study was to explore the associations of demographic characteristics with QOL in children with advanced cancer. Methods: This secondary analysis was part of a larger randomized clinical trial that evaluated the efficacy of a legacy intervention for children (7–17 years) with relapsed/refractory cancer and their primary parent caregivers. Assessments included child self-reports on the Pediatric Quality of Life Inventory (PedsQL) Cancer Module. Researchers used descriptive and linear regression statistical methods. Results: Children ( n = 128) averaged 10.9 years (SD = 3.0). The majority were female ( n = 68, 53%), white ( n = 107, 84%), had a hematologic malignancy ( n = 67, 52%), with family incomes of $50,000 or less ( n = 81, 63.3%). Statistically significant positive associations of both age and income level with PedsQL scores were observed ( p < .05) but not gender ( p > .05). The strongest correlations for age were with the procedural anxiety ( beta = 0.42), treatment anxiety ( beta = 0.26), and total ( beta = 0.28) scores (all p < .01). In general, there was a positive correlation between family income levels and PedsQL scores ( p < .05). The strongest correlations for income were with nausea ( R = 0.49), appearance ( R = 0.44), pain, and treatment anxiety (both R = 0.42) (all p < .01). Associations adjusted for age remained essentially the same (all p < .01). Discussion: Children with advanced cancer with lower family income and younger age are at high risk for poorer QOL. Oncology nurses should seek to identify families who may benefit from additional resources to promote QOL.