A facile one-step electrospraying technology was utilized to produce a novel kind of hollow polyurethane (PU) microspheres with controlled size and tunable surface morphology by adjusting the experiment parameters such as solvent, flow rate, applied voltage, and solution concentration. A porous-hollow structure can be obtained by increasing flow rate or solution concentration, or decreasing applied voltage. The decrease of flow rate or solution concentration, or the increase of applied voltage leads to hollow structures with a non-porous surface. The formation of porous-hollow morphology involves the PU polymer chains deposition during the solvent evaporation process and a phase separation phenomenon induced by the anti-solvent behavior in the water bath. The results demonstrate that the electrospraying method is a novel and facile method for preparing hollow polymer microspheres with tunable surface structures, and the obtained PU microspheres offer diversified applications ranging from adsorbents to drug delivery systems.