Three kinds of Ti-6Al-4V alloy large billet forging processes were developed. Optimization of process parameters by Simufact simulation software. The fullprocess forging was carried out on 10 000 ton hydraulic machine to prepare a large specification forging billet of 245 mm×480 mm×3 700 mm. The mechanical properties and microstructure of the large forging billet were characterized, and the effect of forging technology on the microstructure and mechanical properties of large forging billet was analyzed. The results show that the microstructures of large forging billet Ti-6Al-4V alloy are isoaxial, and the initial alpha phase content account for about 80%. The microstructures of forging billets forged by process A and process B are small and the uniformity is good, and the level of ultrasonic clutter is lower. The forging billet grain size of process C forging is large and uneven tissue, and there are long strips and large block alpha phases in the heart. The forging billets produced by process A and B have a good strength and plastic match. Although the strength of process C is high, but the plasticity is relatively low. Process A is the optimal scheme considering the tissue uniformity, mechanical properties and clutter level.