Background: Quality of life (QoL) is a complicated phenomenon in patients with thalassemia major. This study was conducted to clarify the concept of QoL in patients with thalassemia major. Materials and Methods: This study was performed using Roger’s evolutionary method. Electronic databases: Cochrane Library, Web of Science, Scopus, Science Direct, ProQuest, and Medline. The inclusion criteria were papers published in English up to March 2017 with no time limit for publication. The keywords searched in titles, abstracts, and keywords of the studies included quality of life, health-relatedquality of life, thalassemia, thalassemia major, beta thalassemia, and beta thalassemia major. Results: 67 studies were included. QoL in most studies had been evaluated using the SF-36 and PedsQL. The terms QoL, HRQoL, and QL were used interchangeably in most of the studies. In this concept analysis, HRQoL and well-being were recognized as surrogate terms for the QoL in patients with thalassemia major. The concepts related to the QoL in patients with thalassemia major included satisfaction, indicator of health care, individual’s own view of health, and health status assessment. Five antecedents identified in this concept analysis were: professional figure mainly involved, clinical-care interventions, medicinal and therapeutic approaches and response to them, disease characteristics and presence of comorbidities, ability and characteristics of patient. Seven attributes of the QoL in patients with thalassemia major were objective, subjective, multidimensional, measurable, dynamic, predictable, and processable. Conclusion: Consequences of the concept were effects on physical functioning and improvement of psychological conditions, compliance with regular chelation therapy, iron overload, continuing education, having an appropriate job and marriage, patients’ economic and social status, and finally, motivation and life expectancy.