Quantum anomalous Hall (QAH) insulators have excellent properties driven by fancy topological physics, but their practical application is greatly hindered by the observed temperature of liquid nitrogen, and the QAH insulator with high Chern number is conducive to spintronic devices with lower energy consumption. Here, we find that monolayer FeSIn is a good candidate for realizing the QAH phase; it exhibits a high magnetic transition temperature of 221 K and tunable C = ±2 with respect to magnetization orientation in the y–z plane. After the application of biaxial strain, the magnetic axis shifts from the x–y plane to the z direction, and the effect of the high C and ferromagnetic ground state on the stress is robust. Also, the effect of correlation U on C has been examined. These properties are rooted in the large size of the Fe atom that contributes to ferromagnetic kinetic exchange with neighboring Fe atoms. These findings demonstrate monolayer FeSIn to be a major template for probing novel QAH devices at higher temperatures.