<p>Molecular dynamics simulations are employed to systematically study the effects of grain size and temperature on the mechanical behavior and microstructural evolution of nanocrystalline Ni subjected to tension-compression cyclic loading. The results indicate that for the fine-grained nanostructures (<i>d</i> ≤ 8.6&#xa0;nm), the stress amplitude decreases continuously with increasing cycle number, accompanied by a reduction in energy dissipation capacity. In contrast, the coarse-grained nanostructures (<i>d</i> &gt; 8.6&#xa0;nm) exhibit stable fluctuations in stress amplitude after an initial rapid drop, demonstrating superior fatigue resistance. Microstructural analysis reveals that early cyclic deformation in fine-grained structures is dominated by grain boundary activities, which transition to dislocation-mediated plasticity after a polycrystal-to-single-crystal transformation. Coarse-grained structures retain their nanocrystalline polycrystalline structure throughout cycling, with dislocation slip governing plastic deformation. Furthermore, the polycrystal-to-single-crystal transition occurs in fine-grained samples at all tested temperatures, and the number of cycles required for the transition decreases with increasing temperature. In contrast, no such transition is observed in coarse-grained samples under any temperature condition. This study elucidates the coupling effect of grain size and temperature on the microstructural evolution and macroscopic mechanical response of nanocrystalline Ni under cyclic loading, providing insights into the design and life prediction of high-performance nanocrystalline metals.</p> Graphical Abstract <p></p>