In order to optimize the position of the micro-texture on the negative chamfering edge ball-end milling cutter, the experiment of milling titanium alloy with the negative chamfering micro-texture ball-end milling cutter was carried out. The effects of micro-texture at different placement positions (rake and flank faces of cutting tools) on cutting performance were compared when the cutting depth was 0.3 mm, and the effects of negative chamfering and micro-texture parameters on cutting performance of the cutter were studied. Finally, the negative chamfering and micro-texture parameters were optimized based on genetic algorithm. The results show that the micro-texture of the flank face can improve the cutting performance, and the negative chamfering angle and width have the greatest influence on the cutting performance. The parameter optimization results are: the negative chamfering angle is 10.016°, the negative chamfering width is 199.995 μm, the micro-pit diameter is 49.996 μm, the micro-pit spacing is 174.004 μm, and the micro-pit distance from the edge is 109.993 μm. The above research realizes high efficiency and high-quality machining of titanium alloy.