Abstract: Arsenic trioxide(ATO) has emerged as a promising therapeutic agent in the treatment of non-acute promyelocytic leukemia(non-APL) hematological malignancies. By mechanisms such as inducing tumor cells apoptosis and inhibiting their proliferation, ATO offers a diversified strategy for the treatment of hematologic malignancies. However, the application of ATO is associated with significant toxicity, especially cardiac events, which was posing challenges to its clinical usage. This review focuses on the therapeutic potential, mechanisms of action, and toxicity management strategies of ATO in non-APL hematologic malignancies, trying to provide reference for medical researchers and clinicians to further optimize ATO’s clinical applications for enhanced safety and efficacy.