High-entropy oxides (HEOs) are attractive for lithium-ion batteries (LIBs) owing to their extensive component scope and regulatable electrochemical performance. However, their own the sluggish kinetics hinder their large-scale application. The modification including adjusting the intrinsic activity and structural design is required to compensate for their inherent shortcomings. Here, oxygen vacancies with goal capability are brought in a special hollow multishelled (LiFeCoNiMnCr)2O3 spheres (Li-HEO-HoMS) through an in-situ formed carbonaceous microspheres as templates coupled with the kirkendall effect to expedite the ion/electron transportation and increase structure/electrochemistry stability. Theory combined with experiment reveal the feasible promotion of Li-ions storage, charge transfer, diffusion dynamics and long-term stability from hollow multishelled sphere structure, oxygen vacancies and entropy-stabilizing effect, which conclusively generates reinforced electrochemical performance. Benefit from these synergistic attributes, the Li-HEO-HoMS exhibits outstanding electrochemical property for LIBs with 767.7 mAh g−1 at 1 A g−1 after 500 cycles and still shows a specific capacity of 443.1 mAh g−1 at a high rate of 4 C. The strategy demonstrates the importance of the intrinsic activity and structural design of HEO in tailoring the electrochemical performance.