The aim of this study was to determine the quality of life in children aged 5-18 years with transfusion-dependent thalassemia who have regular transfusion every 2-6 weeks. Data were collected from the children using the Pediatric Quality of life InventoryTM (PedsQLTM) 4.0 Generic Core Scales (Thai version). The result showed that the quality of life of the children on average was good with the mean total summary Health-related Quality of Life (HRQOL) score of 72.57±14.17. The highest HRQOL score was in social dimension. The lowest score was in school dimension with the emotion dimension and the physical dimension scores in the middle. There was no statistically significant difference in the scores when stratified according to patient gender, age, religion, type of diagnosis, iron chelation therapy, levels of baseline hemoglobin, serum ferritin levels, household income or caregiver education and occupation (p<0.05). However, the least scores were found in the subtopic of exercise activity in the physical dimension and the subtopic of absence from class in the school dimension. The adjustment of the blood transfusion regimen to increase the baseline hemoglobin levels and the promotion of effective blood bank service in nearby hospitals to decrease the school absence days may help to improve the quality of life of the patients.