Background: A diagnosis of cancer in children affects the children themselves and their entire family. Cancer treatment places parents under continuous stress and increases their life burdens.; Objective: The aim of this study was to assess the burden level and predictors as perceived by Jordanian parents of children with cancer. Methods: A cross-sectional survey design was used to conduct the study in 2 hospitals. A sample of 264 parents of children with cancer was recruited. Data were collected using 2 instruments: the Zarit Burden Interview and the Hospital Anxiety and Depression Scale. Results: The mean burden score was 38.1 (SD, 16.6), and 75.4% of parents experienced mild to severe levels of burden. Having a chronic disease, financial constraints, high levels of anxiety and depression, a child with advanced cancer, and a child experiencing pain, nausea, and vomiting predicted higher levels of burden. Conclusions: Characteristics of both parents and children affect perceived levels of burden, and thus both should be taken into consideration by healthcare providers, and nurses in particular. Various interventions can be suggested to reduce the parents' burden, including financial support, psychiatric care, and focused management of symptoms. Implications for Practice: Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation, assessment of burden and screening for at-risk parents is of high importance and could be conducted briefly at admission and repeated thereafter. Healthcare institutions may need to offer various types of interventions for parents who are at high risk of burden to improve their quality of life and reduce their suffering.