In this paper, a milling force prediction model considering the Taylor factor is established, and the Ti-6Al-4V milling force predicted by the model under different milling parameters is presented. In the study, the milling experiment of Ti-6Al-4V was carried out, the milling force was collected by the dynamometer, and the microstructure evolution of the milling surface before and after milling was observed by EBSD. Through the comparative analysis of the experimental results and the model prediction results, the reliability of the prediction model proposed in this study was verified, and the influences of the milling parameters on the milling force were further analyzed. Finally, based on the EBSD observation results, the effects of the milling parameters on the microstructure evolution of the milling surface were studied. The results show that both the tangential milling force and normal milling force increase with the increase in the milling depth and feed rate. Among the milling parameters selected in this study, the milling depth has the greatest influence on the milling force. The average errors of the tangential milling force and normal milling force predicted by the milling force model are less than 10%, indicating that the milling force prediction model established in this paper considering Taylor factor is suitable for the prediction of the Ti-6Al-4V milling force. With the change in the milling parameters, the grain structure, grain size, grain boundary distribution, phase distribution, and micro-texture of the material surface change to varying degrees, and the plastic deformation of the milling surface is largely coordinated by the slip.