Aims: To compare the efficacy of hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA)-haploidentical related donors (RD) and unrelated donors (URD) in the treatment of leukemia. Methods: Ninety-three leukemia patients underwent allogeneic HSCT were divided into two groups: 51 cases of RD-HSCT and 42 cases of URD-HSCT. In the RD-HSCT group, a preconditioning regimen with fludarabine (Flu) + busulfan (Bu) + cytosine arabinoside (Ara-C) was used in 42 patients and total body irradiation (TBI) + Flu + Ara-C was used in the remaining 9. Results: In the URD-HSCT group, a modified preconditioning regimen with Bu + cyclophosphamide was used in 35 patients, while the other 7 patients underwent treatment with TBI + Flu. After transplantation, the occurrence rate of grade II-IV acute graft-versus-host disease (GVHD) was 46.0 and 51.2% in the two groups. Likewise, the rate of chronic GVHD was 46.0 and 63.4%, respectively. No significant differences in the occurrence of acute and chronic GVHD were detected between the two groups. The differences in early-stage infection rate after transplantation, recurrence rate, 3-year survival rate, and disease-free survival rate between the two groups were not significant. Conclusion: HLA-haploidentical RD-HSCT with enhanced preconditioning and administration of immunosuppressants showed a clinical efficacy similar to that of URD-HSCT against leukemia, without the risk of increased infection and GVHD.