The present research work shows a simple method to synthesize 3D NiFe2O4 hollow spheres by a hydrothermal route and its application as catalyst for water splitting in an alkaline microfluidic system. The NiFe2O4 was developed by a simple mechanism from the urea hydrolysis reaction and later subjected to a hydrothermal process to carry out a single-step synthesis, obtaining novel 3D hollow nanospheres with doubles, triples and quadruples shells. 3D NiFe2O4 with large surface area and stability showed a catalytic activity for the oxygen evolution reaction (OER) comparable with the commercial material commonly employed IrO2. The NiFe(2)O(4-)based material was used as an anode and cathode in a microfluidic water splitting device, where the H-2 production was 2.5 and 2.7 x 10(-5) mg s(-1) for 3D NiFe2O4 hollow spheres and IrO2-Pt/C, respectively.