The objective of the present study is to fundamentally explore the evolution of deformed structures of CrCoNiSi0.3 medium entropy alloy subjected to high-speed compression deformation with true strains of 0.16, 0.33, and 0.46 (via split Hopkinson pressure bar system, strain rate of ∼6 × 103 s−1, denoted as HSR deformation), and quasi-static compression deformation with true strains of 0.20, 0.30 and 0.50 (via MTS compression system, strain rate of ∼10−3 s−1, denoted as LSR deformation). From the comparison between the results of HSR and LSR samples, it clearly indicates that the formation of deformation nanotwins is promoted under the HSR deformation and enhances the work hardening effect in the early stage of deformation; as the HSR deformation proceeds, the nanotwins effectively provide the dynamic Hall–Petch effect, leading to an increase in flow stress beyond the stress required for HCP phase transformation. The HCP phase also induces a stronger work hardening capacity at the late stage of deformation. Profuse deformation nanotwins and HCP phase promoted by HSR deformation result in a strong work hardening effect. Furthermore, the flow stress of the HSR deformed sample with a true strain of 0.46 is 1536 MPa, which is about 36% higher than that of the LSR deformed sample with the same true strain, 1102 MPa. It is clear that under the HSR deformation, the defect structures including deformation nanotwins and ultra-thin HCP platelets are much more favorably generated, greatly improving the working capacity.