Flower-like hierarchical three-dimensional NiFe layered double hydroxides hollow microspheres (3D NiFe-LDH HMS), as one kind of novel non-noble metal electrocatalysts, have been fabricated in a template-free route for water oxidation. Both of the concentration of ammonium fluoride and the reaction time are adjusted to obtain a series of NiFe-LDH microspheres, with different internal structures from massive to hollow generated during the hydrothermal treatment, which improve the electrocatalytic activity of the NiFe-LDH catalysts towards the evolution reaction of oxygen. The optimized NiFe-LDH-0.4M HMS show the excellent OER performance in alkaline electrolyte with η = 290 [email protected] mA cm−2, and a Tafel slope of 51 mV dec−1, which outperforms the benchmark RuO2 catalyst. The possible reason is attributed to the more exposure of active sites, and fast ion transport resulting from the hierarchical hollow structure.