Abstract: The strengthening mechanisms of high-entropy alloys (HEA) include lattice friction, solid solution strengthening, grain refinement, in situ phase transformation, and nanoscale precipitation. Additionally, the grain boundary types play a crucial role in determining the mechanical performance of HEA. To investigate the effects of grain boundaries on the compression mechanical performance of Al0.3CoCrFeNi HEA and the underlying mechanisms, molecular dynamics simulations were conducted on compression tests involving HEA with different grain boundaries types. The results indicate that the yield strength of Σ11 is the highest, while that of Σ9 is the lowest. This observation is associated with their deformation mechanisms: Σ11 exhibits a dislocation obstruction mechanism, whereas Σ9 is characterized by the stacking fault slip mechanism. Within grain boundaries of types Σ5, Σ7, and Σ9, the deformation is predominantly governed by the stacking fault slip mechanism, which is significantly influenced by the slip angle. A positive correlation is observed between the yield strength and the slip angle. Conversely, in grain boundaries of types Σ11 and Σ13, the dislocation obstruction mechanism plays a dominant role. Moreover, Moreover, among the elemental metals constituting HEA, the trend of maximum yield strength variation across different grain boundaries is similar to that of HEA. However, there are differences in the numerical values of maximum yield strength, which are closely related to the cohesive energy. As cohesive energy decreases, yield strength increases. Furthermore, the study elucidates the relationship between atomic-level Mises stress and energy changes during the deformation process. The research investigates the correlation between different grain boundaries types and the compression mechanical performance of HEA, offering a theoretical foundation for the optimization of HEA microstructural design. This work contributes to the advancement of material design and performance optimization for high-performance HEA in engineering applications.