Abstract: β-thalassemia is a chronic hereditary hemolytic disease caused by mutations or deletions in the β-globin gene. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative approach for transfusiondependent thalassemia (TDT). However, due to limitations in human leukocyte antigen (HLA) matching and and issues such as immune rejection, only a minority of patients can be cured through this method. Gene therapy offers a new potential cure for TDT patients. Gene therapy approaches for β-thalassemia are broadly categorized into two strategies: gene addition and gene editing. This article reviews the two fundamental strategies of gene therapy and their progress in clinical trials, while also discussing the major challenges confronting current gene therapy for β-thalassemia and exploring potential directions for future research.