Abstract: As a traditional Chinese medicine named "Pishuang", arsenic trioxide(ATO) is well-known for its toxicity. Since the 1970s, ATO has become a research hotspot due to its potent clinical therapeutic benefits for acute promyelocytic leukemia(APL) and remarkably improved curative ratio. It has been demonstrated that both ATO and all-trans retinoic acid(ATRA) can specifically degrade the oncogenic protein PML-RARα, thereby the combination regimen can be an effective treatment option for APL patients in clinic. In addition, the ATO/ATRA regimen and the ATO/interferon alpha regimen also showed synergistic effects in the treatment of non-APL acute myeloid leukemia and adult T-cell leukemia, respectively. Moreover, ATO induced the generation of reactive oxygen species and promoted apoptosis in cancer cells. In light of this, ATO combined with Bcl-2 inhibitor or active ingredients of natural medicine can synergistically induce the apoptosis of various hematological tumors. In this paper, the clinical application and research progress of ATO combined regimen in hematological tumors were summarized and prospected based on preclinical and clinical studies.