Objective To investigate the clinical effect of transplantation of haploid hematopoietic stem cells combined with cord mesenchymal stem cells in the treatment of aplastic anemia. Methods From December 2012 to December 2014, 5 cases with aplastic anemia were treated with haploid hematopoietic stem cells combined with cord mesenchymal stem cells transplantation. The MNC, CD34＋cells, GVHD incidence, blood recovery time, changes of related growth factors （like SDF-1α, G-CSF, IL-6, GM-CSF, TPO, SCF）, the improvement of bone marrow nucleated cells protein phosphorylation ERK1/2 and complications were all observed. Results Five patients obtained hematopoietic reconstitution with MNC of 11.27 ×108 cells/Kg and CD34＋ of 4.0 ×106 cells/Kg. The average platelet recovery time was 15 days and the average recovery time of blood cells was 10.4 days. aGVHD of stage III was observed in 3 patients, localized cGVHD was observed in 3 patients, and they were all improved after treatment. Four patients recovered well, one patient died of fungal pneumonia 73 days after treatment. After transplantation, serum SDF-1α, G-CSF, IL-6, GM-CSF, TPO and SCF were significantly improved （P〈0.05）, the expression of phosphorylation ERK1/2 protein of bone marrow nucleated cells was significantly increased （ P〈0.05）. Onenbsp;case of EB viremia, two cases of hemorrhagic cystitis and two cases of fungal pneumonia were observed. Conclusion Haploid hematopoietic stem cells combined with cord mesenchymal stem cell transplantation is effective in the treatment of aplastic anemia, it can significantly improve the bone marrow microenvironment of patients with higher safety and lower complication. It is worthy of further clinical application.