Abstract: β-Thalassemia is an inherited hemolytic anemia caused by defects in the β-globin gene. β-Thalassemia major results from homozygous or compound heterozygous β⁰ or β⁺ mutations. The 8p11 myeloproli-ferative syndrome(EMS) is a myeloproliferative neoplasm associated with gene translocation of fibroblast growth factor receptor 1(FGFR1) on the short arm of chromosome 8(8p11). BCR-FGFR1 represents a specific fusion gene subtype of this syndrome, which tends to progress to leukemia with a poor prognosis. Allogeneic hematopoietic stem cell transplantation(allo-HSCT) is currently the only therapeutic approach expected to achieve long-term remission. This article reports, for the first time in the world, a case of pediatric EMS arising in the context of β-thalassemia major. The patient developed EMS driven by the BCR-FGFR1 fusion gene. Conventional cytogenetic analysis revealed, for the first time, an atypical translocation, t(8;21)(p11.2;q11.2), accompanied by a secondary deletion del(22)(q13). Although BCR-FGFR1 fusions have been well documented, this precise molecular configuration and its associated cytogenetic background have not been described to date. Given the lack of established therapeutic experience in patients with concurrent β-thalassemia major and EMS, strategies were formulated in line with mainstream international regimens and current clinical guidelines. The patient received intensive chemotherapy combined with early allo-HSCT, resulting in gradual clinical improvement. At 47 months posttransplantation, the patient remains in good general condition. The findings of this study expand the molecular spectrum of FGFR1-driven neoplasms and provide novel clinical insights into the management of thalassemia complicated with hematologic malignancies. Furthermore, we review potential mechanisms underlying the development of hematological malignancies in thalassemia major patients and underscore the pivotal role of high-resolution genomic profiling and allo-HSCT in achieving durable remission.