Acute myeloid leukemia (AML) with NUP98-HOXA9 fusion gene is rare, which is caused by t(7;11)(p15;p15). Not only the prognosis is poor, the efficacy of conventional induction regimen is also barely satisfactory. Here we report two cases of NUP98-HOXA9 bearing AML. Patient 1 was a 54-year-old female. In September of 2019, she felt fatigue with complete blood count (CBC) result of leukocytes 246.78× 109/L, hemoglobin 81g/L, and platelet 119 × 109/L. Peripheral blood smear showed 5% blast cells, and bone marrow (BM) smear demonstrated AML-M5. Chromosome 46, XX, t (7; 11) (p15; p15) [20], NuP98/HOXA9 fusion gene, EVI1 expression, FLT3-ITD and KRAS mutation was also found in her BM. One course of standard induced chemotherapy regimen IA reached CR, with MRD<10-4, low expression of EVI1, and FLT3-ITD(-),normal chromosome, but NuP98/HOXA9(+). After the second course of IA, relapse occurred partly due to delayed admission under the influence of COVID-19. Reinduction with IA, azacytidine +HE, FLAG regimen failed to reach remission, and the patient died of bone marrow suppression and gastrointestinal bleeding. Patient 2 was a 65-years-old male. In September of 2019, he suffered from fatigue and CBC showed leukocytes 2.52× 109/L, hemoglobin 36g/L and platelet 139 × 109/L. Peripheral blood smear showed immature cells of 7%, and his BM smear demonstrated AML-M4. Chromosome 46, XY, t (7; 11) (p15; p15) [18]/46, XY[1], NuP98/HOXA9 fusion gene and IDH2 R140Q mutation were found in the patient. He had a history of chemotherapy for small cell lung cancer. After induced by regimen of DIAG, DHEG and DCAG successively, he did not reach remission. Repeated fever and lung infection occurred during the course of the disease. He was discharged automatically due to the progression of lung cancer. NuP98/HOXA9 bearing AML is more common in young Asian women, and the majority is type M2. The two patients in this report were older with M4 or M5 type, which was rare in this kind of leukemia. NuP98/HOXA9 is a poor prognostic factor for AML. Patient 1 could reach cytogenetic CR after IA induction, relapsed before transplantation, and the effect of reinduction therapy was poor; Patient 2 did not achieve remission. It is suggested from the these patients that patients with NuP98/HOXA9 bearing AML should undergo hematopoietic stem cell transplantation as soon as possible after CR with intensive therapy if their physical conditions permit.