Introduction: Self-care is the core concept of health care and may be considered as one’s stabilization, and restoration as well as the improvement of his/her health and well-being. Looking at the process of Self-care from patients’ perspective who suffer from thalassemia may assist the nurses and health care providers to facilitate the health process. Thus this study was conducted to discover the process of self-care in patients with major thalassemia. Methods: This qualitative study was conducted with grounded theory approach. 21 patients with major thalassemia from a Medical Research Center, supervised by Kerman Medical University, were selected through purposeful and theoretical sampling. Data were collected by unstructured interviews which lasted 30-60 minutes. These data were analyzed using the method of Corbin and Strauss. Results: The main theme of "struggling to improve life quality" that included the sub-themes of "focus on needs of illness, "activating resources" and "restoring a new identity with thalassemia" were extracted from the data. This theme implies that participants endeavor to strengthen their self- efficacy via thalassemia. "Looking for strengthening self-efficacy in light of thalassemia" was the core theme in this study. Conclusion: Facilitating the process of self-care in patients with major thalassemia requires that they be helped so that their self-efficacy, influenced by real life conditions, might be strengthened in light of thalassemia. Increasing public awareness and social support may affect the recognition of individual, family and society.