The treatment of refractory autoimmune hemolytic anemia (AIHA) in childhood remains a significant challenge in hematology practice. Steroids, intravenous immunoglobulin (IVIG), rituximab, various immunosuppressants, and chemotherapeutic agents are commonly used. In highly refractory cases, hematopoietic stem cell transplantation may even be considered. Here, we describe a pediatric AIHA case that was highly refractory to conventional therapies but responded dramatically to bortezomib without any adverse effects. The patient showed a remarkable recovery starting from the first doses of the drug. Bortezomib may be considered as an alternative treatment option in such cases.