Sintering of metal nanocatalysts leading to particle growth and subsequent performance deactivation is a primary issue that hinders their practical applications. While metal-support interaction (MSI) is considered as the critical factor which influences the sintering behavior, the underlying microscopic mechanism and kinetics remain incompletely understood. Here, by using scanning transmission electron microscopy (STEM) and theoretical analysis, we reveal the selection rule of the sintering mechanism for Pt nanoparticles on a two-dimensional (2D) MXene (TiCT ) support, which relies on the surface topology of MXene flakes. It is demonstrated that the sintering of Pt nanoparticles proceeds Ostwald ripening (OR) in the surface defect (such as steps and pore edges) regions of MXene flakes due to strong MSI on the Pt/MXene interface; conversely, weak MSI between Pt nanoparticles and the planar surface of MXene leads to prevalent particle migration and coalescence (PMC) for sintering. Furthermore, our quantitative analysis shows a significant divergence in sintering rates for PMC and OR processes. These microscopic observations suggest a clear "sintering mechanism-MSI" relationship for Pt/MXene nanocatalysts and may shed light on the design of novel nanocatalysts.