Abstract: Aluminum nitride (AlN) is an ideal material for the thermally conductive fillers in thermal interface materials due to its excellent thermal conductivity and electrical insulation. The surface modification of the AlN powders was firstly carried out to improve the hydrolysis resistance of AlN powders in this paper, then the spray granulation was carried out using the water-based solvents. The process parameters, such as ball milling time and binder dosage, were optimized during the slurry configuration. The AlN spherical fillers with high sphericity were prepared. Finally, the AlN fillers with low oxygen content, high sphericity, and high thermal conductivity were fabricated by debinding and sintering. In the results, the phosphoric acid-modified AlN powders can maintain the good hydrolysis resistance after the ball milling for 16 h. The binder content (mass fraction) has the significant effect on the green shape after the spray granulation. The powders prepared with 2% PVB+2% PEG binders show the good sphericity and surface smoothness. After debinding and sintering, the thermal conductivity and flexural strength of the AlN ceramic microspheres reach 171.2 W·m⁻¹·K⁻¹ and 340 MPa, respectively, showing the good fluidity. In conclusion, the water-based spray granulation is suitable for the preparation of high thermal conductivity spherical aluminum nitride fillers.