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Background Besides the traditional roles of HBA1 and HBB, recent findings suggest that hemoglobin genes may have roles in other contexts.Objective In the present study, we aim to investigate a possible tumor-suppressor role of HBA1 and HBB in acute myeloid leukemia.Methods Quantitative real-time PCR (RT-qPCR) was performed to detect the expression levels of HBA1 and HBB in acute myeloid leukemia patients and AML cell lines. The transfected cells were analyzed for Cell Counting Kit-8 (CCK-8), apoptosis, and cell cycle assay.Results HBA1 and HBB genes were significantly decreased in acute myeloid leukemia patients and AML cell lines. Furthermore, in vitro approaches showed that overexpression of HBA1 and HBB inhibited proliferation, induced cell apoptosis, and blocked cell cycle process at the G2/M phase in K562 cells.Conclusion Our data indicated that HBA1 and HBB genes may be potential tumor-suppressor genes in acute myeloid leukemia.