Objective To investigate and analyze the efficacy of dual-membrane filtration plasma exchange (DFPP) combined with desensitization therapy in the treatment of donor-specific antibodies (DSA) in haploid matched hematopoietic stem cell transplantation patients.  Methods  The DSA-positive patients were desensitized with DFPP, intravenous immunoglobulin (IVIG) and rituximab. The DSA levels before and after transplantation were measured. The incidence of implantation and graft-versus-host disease (GVHD) were evaluated and analyzed.  Results  Seven of the eight DSA patients received stable implantation of donor cells with the chimerism rate of 100%, and one patient had poor platelet implantation. After desensitization with DFPP, IVIG and rituximab, the mean fluorescence intensity (MFI) reduced to 3911±2499 (t=2.101, P＜0.000); 3 of the 8 patients turned to be weak positive. The MFI reduced further to 907±997 after stem cell reinfusion for 3 days, significantly lower than that before stem cell reinfusion (t=2.145, P=0.002). Only one of the 8 patients developed severe acute GVHD.  Conclusion Dual-membrane filtration plasma exchange combined with the desensitization therapy of high dose IVIG and rituximab can reduce the level of DSA and promote the implantation of donor stem cells.