Primary immunodeficiency disease (PID) is a rare monogenic hereditary disease with severe clinical manifestations and high mortality. Early diagnosis and complete immune reconstitution in a timely and effective manner is the key to prognosis. Nowadays, gene therapy is still in the experimental stage, and hematopoietic stem cell transplantation is currently the only means of reconstructing immunity. TCRαβ T cell/B cell-depleted hematopoietic stem cell transplantation as a novel T-cell-free transplantation strategy has been gradually used in the radical treatment of primary immunodeficiency disease in children in recent years. It has achieved satisfactory results in the prevention and control of graft-versus-host disease and the reduction of post-transplant infection. This article reviews its biological basis and recent progress.