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Plastic deformation mechanisms at micro/nanoscale of graphene oxide-reinforced high-entropy alloy composites (HEA/GO) remain unclear. In this study, small-scale mechanical behaviors were evaluated for HEA/GO composites with 0.0 wt.%, 0.3 wt.%, 0.6 wt.%, and 1.0 wt.% GO, consisting of compression testing on micropillar and molecular dynamics (MD) simulations on nanopillars. The experimental results uncovered that the composites exhibited a higher yield strength and flow stress compared with pure HEA micropillar, resulting from the GO reinforcement and grain refinement strengthening. This was also confirmed by the MD simulations of pure HEA and HEA/GO composite nanopillars. The immobile <100> interstitial dislocations also participated in the plastic deformation of composites, in contrast to pure HEA counterpart where only mobile 1/2 <111> perfect dislocations dominated deformation, leading to a higher yield strength for composite. Meanwhile, the MD simulations also revealed that the flow stress of composite nanopillar was significantly improved due to GO sheet effectively impeded dislocation movement. Furthermore, the mechanical properties of HEA/1.0 wt.% GO composite showed a slight reduction compared with HEA/0.6 wt.% GO composite. This correlated with the compositional segregation of Cr carbide and aggregation of GO sheets, indicative of lower work hardening rate in stress-strain curves of micropillar compression.