A microwave-hydrothermal (M-H) method assisted with ultrasonic atomization precipitation was developed for large-scale and fast synthesis of nano-hydroxyapatite (nano-HAP) powder. This technology combines the uniform mixing effect of ultrasonic atomization precipitation at high concentration with the rapid and uniform heating effect of the M-H method, aiming to obtain a high quality product with low agglomeration, homogeneous size distribution, accurate stoichiometry, and high purity while improving the yield. The influences of reaction temperature, reaction time and reactant concentration on the formation of nano-HAP were investigated. The results show that the crystallinity increases significantly and the diameter of nano-HAP increases to some extent, but the length does not change obviously while the reaction temperature increase from 60 °C to 160 °C and the reaction time increases from 1 minute to 40 minutes respectively. The crystallinity, dispersion and crystal size of nano-HAP do not change obviously while the concentration of Na₂HPO₄·12H₂O increases from 0.06 mol L⁻¹ to 0.4 mol L⁻¹. When the reaction temperature is 160 °C, the reaction time is 40 min, and the concentration of Na₂HPO₄·12H₂O is 0.4 mol L⁻¹, the yield of nano-HAP powder achieved a maximum yield (0.033 kg L⁻¹). The obtained nano-HAP powder exhibits a uniform size and good dispersibility, with a size of 87.62 ± 22.44 nm and crystallinity of 0.92, respectively. This study indicates that the M-H method assisted with ultrasonic atomization precipitation is a facile one-pot method for the rapid and large-scale synthesis of highly crystalline, dispersible nano-HAP particles.