Background: The cyclophosphamide (Cy) based conditioning regimen is commonly used in allogeneic HSCT. Acute Cy-induced cardiotoxicity after HSCT was rare, it may progress to rapidly fatal congestive heart failure. Cytokine Release Syndrome (CRS) frequently complicates the immediate post-peripheral blood haploidentical Hematopoietic Stem Cell Transplantation (HSCT), a small percentage of patients developed severe (grade 3-4) CRS, which was associated with a significantly higher transplant-related mortality and frequently required intensive care unit treatment. Case presentation: We report a young child of severe aplastic anemia who received allogeneic HSCT. At days +3 after HSCT or 120 hours after the last dose of Cy, she experienced both post-transplant grade 4 CRS and Cy-associated fatal cardiotoxicity. She was admitted to the hematology intensive care unit (HCU) and treated with glucocorticoids and tocilizumab, but remained severe syndrome including fever, shock, multiple organ damage and insufficient tissue perfusion. She subsequently underwent continuous veno-venous hemofiltration combined with cytokine adsorption at day 3 of HCU, and her condition gradually improved. Conclusion: Overall, this case highlights the critical importance of maintaining a high attention and careful evaluation of severe complications immediate post-HSCT, and timely intervention can potentially offer the survival opportunity