Purpose: to predicate the way in which families incorporate the work of managing a child with thalassemia within family life and its outcomes. Methods: A correlational design was used. The structural equation modeling (SEM) approach was used. A total of 309 parents of children with thalassemia from four tertiary care hospitals in Thailand complete our questionnaires. Results: Family life difficulty had a negative influence on child HRQOL(b = - 4.3, p < .05) and family functioning (b = - 2.72, p < .05), whereas child’s daily life (b = 4.18, p < .05) and condition management ability(b = - 2.8, p < .05) had a positive influence on child HRQOL. In the final model, three variables including child’s daily life, condition management ability, and family life difficulty could explain 33% of variance of child HRQOL (R2= 0.33). Also this model showed that only family life difficulty could explain 2% of variance of family functioning (R2 = 0.02). Conclusion: The study results suggested that nurses should design interventions to support families in managing their child conditions in order to achieve a child and family outcomes.