Here we demonstrate high-performance ethanol sensors based on Fe-doped In2O3 mesoporous nanospheres. By using FDU-12 as template via a facile one-step impregnation method Fe-doped In2O3 were synthesized, which display high surface area, uniform shape, ordered mesoporous structure and small particle size. The Fe-doped In2O3 exhibited a larger response to ethanol gases than pure In2O3 under all measured concentrations. Furthermore, the effect of Fe/In molecular ratio on sensing property was investigated by comparing their response. The enhanced sensing properties could result from the unique mesoporous structure and the synergic electronic interaction between the guest Fe dopant and the host In2O3 material.