Background Asthma is a common disease in Egypt that puts a serious burden on children’s health related quality of life (HRQOL) and their primary caregiver. Objectives To assess HRQOL of asthmatic children and their caregivers and identify the most important determinants that adversely affect (HRQOL) of them. Methods This cross sectional study included 112 pairs of asthmatic patients (7 - 17 years old) and their primary caregivers attending the Outpatient Pediatric and chest Clinics at Benha University and chest Hospitals. Pediatric Asthma Quality of Life Questionnaire, Pediatric Asthma Caregiver's Quality of Life Questionnaire, asthma control questionnaire and questionnaire of main determinants of asthma were used. Results The overall PAQLQ score ranged between 1.27 and 5.73 (3.271.05) and the overall PACQLQ score ranged between 1.18 and 5.85 (3.211.17).There was significant positive correlation between (caregiver individual and overall QOL scores) and their children (individual and overall QOL scores). Maternal educational level, social score and asthma control score were the determinants of overall PAQLQ score for asthmatic children (95% CI = -0.79±-0.04, 0.03±0.08, -0.33±-0.004 respectively, R2 = 0.46). Social score, asthma control score of the children and parental smoking were the predictors of overall caregiver QOL score (95% CI = 0.003±0.06, -0.40±0.01, -1.09±0.04 respectively, R2 = 0.32). Conclusion Childhood asthma significantly adversely affects the QOL of the affected children and their caregivers.