Abstract: In recent years, haploidentical hematopoietic stem cell transplantation (haplo- HSCT) has been widely used. At present, there are urgent clinical challenges that need to be solved: how to reduce the incidence of graft-versus-host disease (GVHD), manage the complications of transplantation, and improve the quality of life of the patients? Co-transplantation of umbilical cord blood and haploidentical hematopoietic stem cells has been gradually carried out in some centers at home and abroad. It could overcome the limitations of haplo-HSCT and umbilical cord blood stem cell transplantation and retain the effect of haploidentical grafts on leukemia. Co-transplantation shows certain curative effects and has potential applications in accelerating hematopoietic reconstruction and reducing the incidence of GVHD. Co-transplantation could achieve curative effects similar to those of human leukocyte antigen (HLA)- matched transplantation. This review summarizes the efficacy and influencing factors of this co-transplantation regimen and summarizes the issues of viral infection, immune reconstitution, and hematopoietic chimerism after transplantation, to provide a reference for extending the clinical application of this regimen in the future.