The arsenic compounds including arsenic trioxide and arsenic sulfide have played a crucial role in the clinical treatment of hematologic malignancies and solid tumors. Arsenic agents can induce tumor cells differentiation, apoptosis and autophagy, eliminate leukemia-initiating cells, and directly bind to the target proteins. This paper reviews the mechanism progress of arsenic agents in various tumors to further understand the intricate anti-tumor mechanisms of arsenic agents and to expand its therapeutic spectrum.