The hardness and plastic deformation behavior of single-phase concentrated solid solution alloy CoCrFeNi were studied for selected crystallographic orientations (⟨001⟩, ⟨011⟩ and ⟨111⟩) using Berkovich nanoindentation. The integration of transmission electron microscopy (TEM) and molecular dynamics (MD) simulations was carried out to elucidate comprehensively the distinction in the deformation mechanisms, the evolution of dislocation structures, and the pile-up of differently oriented CoCrFeNi alloys subjected to indentation by a Berkovich indenter. In MDs, a Berkovich indenter, meticulously crafted to replicate its real geometry, was effectively employed in investigating the nanoindentation. The ⟨001⟩-oriented CoCrFeNi exhibited the highest hardness and the lowest magnitude of pop-in events, followed by the ⟨011⟩ and then the ⟨111⟩ orientations. The pile-up behavior was strongly dependent on the crystallographic orientation and occurred by three sequential processes. The deformation twinning was activated only in the ⟨001⟩ orientation and inclined toward the center direction of the indent due to the force inclining toward the radial direction of the indent. The clear manifestation of the evolution of dislocations in the three orientations during indentation was elucidated. More SFTs or Stair-rods were observed in the ⟨001⟩ orientation, attributable to the intensified reaction of Shockley partials stemming from its higher density of Shockley partials, followed by the ⟨011⟩ and then the ⟨111⟩ orientations. The anisotropic nanoindentation-hardness was correlated with the microstructures. The highest hardness and lowest magnitude of pop-in events of the ⟨001⟩ orientation could be ascribed to its intense dislocation interactions, high-density SFTs and the formation of twins. In the ⟨111⟩ orientation, the three-fold symmetry emission of prismatic dislocation loops along the three slip directions not parallel to the surface leaded to a weak interaction between dislocations, and then resulted in the lowest hardness. This research may be helpful to enhance our comprehension of the intricate mechanical behaviors exhibited by different oriented FCC high entropy alloys under Berkovich indentation.