The circular-hole rotating core fog nozzle has excellent atomization performance and has been widely used in the realm of spray dust. As part of this study, a mathematical model was developed for predicting the Sauter mean diameter (SMD) of nozzles of this type. The coaction between the SMD of the nozzle and the three influencing factors of axial distance, water supply pressure, and outlet diameter was investigated based on the customized spray’s experimental platform and orthogonal design method. According to the comparative analysis of the size range, the axial distance, outlet diameter and water supply pressure are three parameters that affect the SMD of the nozzle, and the degree of influence is axial distance > outlet diameter > water supply pressure. On this basis, a mathematical model was developed using the multiple regression method to predict the SMD of the nozzle. We analyzed the results and compared them to the SMD value predicted by the multiple regression mathematical model and the orthogonal experiment results. The change trend was the same, the values were essentially the same, and the average relative error was just 16.11%. Accordingly, the mathematical model presented in this paper may be used for the prediction and calculation of the droplet size for circular-hole rotating core micro-fog nozzles.