Ti-6Al-4V(TC4)has been the most highly used titanium alloy, and it is the world leading in the applications of titanium alloys. In this paper, mechanical alloying is adopted to prepare Ti-6Al-4V alloy powder, the experimental results show that: mechanical alloying can prepare nanocrystalline Ti-6Al-4V alloy powder, the reaction mechanism dominated by diffusion, and the solid-state reaction is the result of defects in energy and interaction of the collision energy. With increasing milling time, substitution solid solution Ti(V)formed in the process, there is no intermediate phase generated in milling process. After milling for 40h can obtain nanocrystalline, nanocrystalline and polycrystalline mixtures obtained for 60 hour. The grain sizes are less than 60nm and little change in grain size after milling for 60h. After milling, the atomic ratio of Ti, Al, V is near to 90:6:4, which is consistent with the Ti-6Al-4V elemental composition.