A novel lysine-assisted hydrothermal process is first developed to produce hierarchically porous Fe2O3 microspheres assembled by well-crystalline nanoparticles. The fabrication process is very simple, without employing any surfactants or templates. A possible growth mechanism of the nano/microspherical superstructure is further discussed. The contribution of lysine to the formation of the unique microspheres is also tentatively proposed. Furthermore, as an anode electrode material for rechargeable lithium-ion batteries, the Fe2O3 microsphere displays excellent electrochemical performance. It also exhibits the feature of capacity increase upon cycling and shows a stable and reversible capacity of 705 mA h g−1 after 430 cycles. The outstanding electrochemical performance of the Fe2O3 microsphere can be attributed to the hierarchical porosity, ordered microstructure, good electron pathways and easy penetration of the electrolyte.