Hollow 0.3Li(2)MnO(3)·0.7LiNi(0.5)Mn(0.5)O(2) microspheres are synthesized on a large scale through a simple in situ template-sacrificial route. Starting from porous MnO(2) microspheres, the hollow microspheres assembled with 0.3Li(2)MnO(3)·0.7LiNi(0.5)Mn(0.5)O(2) nanocrystals are formed by a nanoscale Kirkendall effect. The nanocrystal-assembled hollow 0.3Li(2)MnO(3)·0.7LiNi(0.5)Mn(0.5)O(2) microspheres exhibit a highly reversible capacity as high as 295 mAh g(-1) over 100 cycles and excellent rate capability (125 mAh g(-1) at 1000 mA g(-1)). Benefitting from a unique hollow and nanocrystalline architecture, the as-formed hollow microspheres show much enhanced high-temperature (55 °C) electrochemical performances, compared with the products obtained by conventional sol-gel/solid-state reaction methods. This work demonstrates that a fabrication strategy based on the present in situ template-sacrificial approach offers a new method for the design of high-performance cathode materials with hollow interiors for Li-ion battery applications.