ABSTRACT: OBJECTIVES:To identify the association of multiple symptoms and clinical characteristics on quality of life (QoL) of paediatric patients with cancer. DESIGN:A descriptive, cross-sectional study. SETTING:South American Children's Hospital for Cancer Treatment (Barretos, São Paulo, Brazil). PARTICIPANTS:A total of 157 participants, 116 paediatric patients, diagnosed with cancer, undergoing chemotherapy treatment, between 7 and 18 years of age and 41 proxies for patients between 2 and 6 years of age. PRIMARY OUTCOME MEASURES:The severity and prevalence ofsymptoms were identified through the use of a culturally adapted multi-symptomscreening tool, and the influence these symptoms, in association with clinicalcharacteristics, had on the QOL of Brazilian pediatric cancer patients wasassessed. RESULTS:Prevalent symptoms identified by all participants were 'feeling tired' (98, 62.4%), 'feeling more or less hungry (do not feel like eating) than you usually do' (96, 61.1%), 'changes in taste (flavour of the food)' (89, 56.7%), 'throwing up or feeling like you may throw up' (77, 49%) and 'changes in how your body (visually) or face looks' (72, 45.9%). The multivariate analysis for symptom severity as reported by proxies showed that surgery (OR 0.20, 95%?CI 0.04 to 0.98, p=0.047) and time of diagnosis (OR 0.14, 95%?CI 0.03 to 0.66, p=0.012) were associated with a decreased OR of high severity symptoms.An analysis of the clinical characteristics associated with Pediatric Quality of Life Inventory (PedsQL) demonstrated no significant effect on QoL in any of the domains evaluated. The association between Symptom Screening in Pediatrics Tool and PedsQL in the self-report version demonstrated a significant negative influence of all symptoms on the QoL. CONCLUSIONS:The prevalence of symptoms experienced among pediatric patients during treatment was high and significantly influenced all aspects of quality of life,especially in the emotional domain.