Co-free high entropy spinel oxide (HESO) with all metals being active for use as anode in Li-ion battery (LIB) is demonstrated for the first time. The HESO, (CrMnFeNiCu)3O4, was synthesized via a simple and scalable hydrothermal method followed by post annealing at temperatures ranging from 800 to 1000 °C. The post annealing provides a simple way to control the particle size and crystallinity. As a result, the missing link between the anode performance and the critical factors of particle size and crystallinity/phase is reported for Co-free high entropy oxide. The HESO anode with balanced crystallinity and particle size displays optimized electrochemical performance. It shows excellent cycling stability (∼99%) after 250 cycles and the excellent rate capability. The structure evolution during cycling was examined using in operando XRD, indicating the existence of nano-crystalline structure after the lithiation/delithiation reactions. This feature is favorable for enhancing electrode cyclability. This study thus opens a new window of opportunity for the development of next-generation LIB electrode materials.