Abstract: Three interlayer temperature control schemes of continuous welding, welding next layer after welding layer was cooled to room temperature, welding next pass after welding pass was cooled to room temperature, and two annealing temperatures of 730, 600℃ were selected, and the optimal process of gas tungsten arc welding (GTAW) for large-thickness TC4 titanium alloy cast plate was determined by microstructure, tensile properties and fatigue properties. The mechanical properties of welded joint under the optimal process were studied. The results show that the welded joint by welding next layer after welding layer was cooled to room temperature had the smallest weld microstructure and the highest fatigue life, and the welded joint after annealing treatment at 730℃ had better tensile properties; so they were determined as the optimal process. Under the optimal process, the hardness of weld of the GTAW joint was slightly higher than that of base metal, and the joint was a highly matched joint. The joint fractured at base metal during both tension and fatigue processes, but the fatigue cracking resistance of the weld was lower than that of base metal.