This study investigates the mechanical responses and deformation mechanisms of CoCrFeMnNi high-entropy alloy (HEA) with varying grain size gradients through molecular dynamics simulations, and explores the tension-compression asymmetry of gradient nanograined high-entropy alloy (G-HEA) under different loading conditions. In the early stage of plastic deformation, the normal stress and shear strain of G-HEA both exhibit gradient distribution characteristics under compression and tension. However, as the engineering strain increased, these gradient distribution characteristics gradually diminished and ultimately disappeared. Grain boundary (GB) migration and grain merging are the main GB activities of G-HEA, and fine grains in the soft zone have stronger grain boundary vitality compared to coarse grains in the hard zone. G-HEA exhibits multiple plastic deformation mechanisms, including dislocation slip, deformation twinning, and hexagonal close-packed (HCP) phase transformation. There are both synergy and competition among various deformation mechanisms, which collectively enhance the mechanical properties of materials. This work has found that the differences in GB activities are the main cause of stress and strain asymmetry in G-HEA, while the different nucleation positions of dislocations are the reasons for the asymmetry in dislocation density, yield stress, and average flow stress. In addition, when