Background Reports of acceptability of psychosocial screening are limited, and the utility of screening in identifying risk factors for health‐related quality of life (HRQL) of children with cancer has not been established. This study aimed to assess acceptability of screening for parents and evaluate associations between family risk factors and patient HRQL in the first year post‐diagnosis. Procedure Sixty‐seven parents of children with cancer completed the Psychosocial Assessment Tool (family risk), Distress Thermometer (caregiver distress), Posttraumatic Stress Disorder Checklist‐Civilian 6 (caregiver traumatic stress), PedsQL 4.0 (parent‐proxy report of patient HRQL) and four acceptability questions via a tablet (iPad). Results Patients (Mage = 9.5 SD = 5.5 years) were equally distributed across major pediatric cancer diagnoses. The majority of parents endorsed electronic screening as acceptable (70%–97%). Patient gender, diagnosis, intensity of treatment and time since diagnosis were not significantly correlated with family risk, caregiver distress, traumatic stress, or patient HRQL. The full regression model predicting total HRQL was significant (R2 = .42, F(4,64) = 10.7, p = .000). Age (older) was a significant covariate, family risk and caregiver distress were significant independent predictors of poorer total HRQL. The full regression models for physical and psychosocial HRQL were significant; age and caregiver distress were independent predictors of physical HRQL, and age and family risk were independent predictors of psychosocial HRQL. Conclusions Screening is acceptable for families and important for identifying risk factors associated with poorer patient HRQL during childhood cancer treatment. Targeted interventions addressing family resource needs as well as parent distress identified through screening may be effective in promoting patient HRQL. Copyright © 2016 John Wiley & Sons, Ltd.