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In the present study, V₁₀Cr₁₅Mn₅Fe₃₅Co₁₀Ni₂₅ (at%) high-entropy alloy (HEA) of a single phase face-centered cubic structure with various grain sizes was fabricated. The influences of grain size on the work-hardening behavior and deformation mechanisms were investigated. The fine-grained and coarse-grained samples showed different work hardening behaviors during room temperature tensile deformation. Microstructural analysis revealed the presence of a high-density tangled dislocation structure without any mechanical twinning in the fine-grained sample, while mechanical twinning was observed to be the additional deformation mechanism in the coarse-grained sample.