Introduction: Thalassemia is the most common inherited disease in the world and Iran. Many physical, mental, psychological, economic and social problems in these patients affected their quality of life. This study aimed to compare the health-related quality of life in beta thalassemia major and healthy people in dezful in 2015. Method: In this descriptive-analytic study 112 patients with thalassemia major referred to thalassemia major clinic of dezful large hospital and 130 healthy people of the same age and sex were selected for comparison. The SF-36 was used to measure the quality of life. Data were analyzed using SPSS software version 18 and T-test and Pearson correlation coefficient. Results: There was no statistically significant difference between age average in two groups (p=0/027). Physical health scores were higher than mental health scores in patients. public health, emotional welfare, energy/fatigue, role disorder related to physical health, role disorder related to emotional health, social functioning, physical health, mental health and quality of life scores were significantly different between two groups(P<0/05). But no significant difference in pain between two groups (p=0/48). Patients with thalassemia compared to healthy people had better physical functioning and this difference was statistically significant (P=0/03). Conclusion: According to the results seems thalassemia people knew developing to this disease equal to feelings of hopelessness and worse health status than other people that would reduce their general health and quality of life. Lower scores of the mental health of these patients and needing to better compliance with their disease demand psychological counseling services and psychosocial support.