AbstractThe challenges of parental cancer while caring for young offspring are often neglected by researchers and healthcare providers. Focusing on parents with cancer, this cross-sectional study examines the mediating and moderating roles of a malleable risk factor, psychological inflexibility, in the relationships between perceived illness severity and parental quality of life (QoL) and family outcomes. Psychological inflexibility was conceptualized using the acceptance and commitment therapy (ACT) framework. A total of 86 parents with cancer caring for young offspring (aged 11–24 years; M = 17.94, SD = 3.68) completed a survey that assessed psychological inflexibility, parental mental and physical health QoL, family outcomes (family functioning, parenting concerns, and openness to discuss cancer), socio-demographics, and illness variables. Mediation analyses indicated that higher perceived illness severity was associated with higher levels of psychological inflexibility, which in turn were related to higher detrimental impacts on parental QoL and family outcomes. Results of moderation analyses were non-significant. Findings highlight the detrimental impacts of illness severity on psychological inflexibility, suggesting that it is a psychosocial risk factor in parents dealing with cancer. ACT-based interventions which foster psychological flexibility are likely to enhance parental QoL and family outcomes.