The study was aimed to explore the efficacy and safety of allo-HSCT with high-dose cyclophosphamide-induced immune tolerance for SAA. In the present study, 20 cases (12 male, 8 female; average age = 17.8 years) received reduced-intensity conditioning allo-HSCT from August 2012 to August 2014 in the Beijing Military Region General Hospital. All were HLA mismatched and received CSA; 11 received ATG-intensive immune therapy. Donors underwent mobilization with cell colony-stimulating factor. The modified preconditioning regimen included reduced-strength fludarabine combined with Busulfex and cytarabine, cyclophosphamide. Cyclophosphamide (50 mg/kg/d) induced immune tolerance 3 days after transplantation and was combined with immunosuppressive agents, including CSA, MTX, and FK506, for GVHD prophylaxis and the management of observed toxicity, GVHD and DFS. Hematopoietic reconstitution was achieved in 17 cases and engraftment after a second transplantation in an additional three cases. The average times to engraftment were 17.4 and 21.3 days, respectively, with neutrophils ≥0.5 × 109/L and platelets ≥20 × 109/L. Engraftment was confirmed by the evidence of 100 % donor hematopoiesis; T lymphocyte subset counts also increased significantly after transplantation. During follow-up monitoring to April 2015 (median duration = 17.7 months), three patients died of complications, while the other 17 showed disease-free survival (DFS rate = 85 %; longest DFS period = 32 months). Reduced-intensity allo-HSCT with high-dose cyclophosphamide-induced immune tolerance treatment is effective for SAA and can be the key technology extensively used in clinic, but its efficacy needs to be confirmed further with prospective randomized study with increased sample size.