This paper deals with the simulation of rotary piercing process of Ti80 alloy seamless tube via a 3D thermal-mechanical coupling model. The model can visualize the complex continuous piercing process from biting to steady piercing and to final drilling. Concurrently, the simulated result helps to understand the central fracturing and physical fields distribution. Combining the stress state of (+, -, +) along the rolling centerline with non-negligible plastic deformation at the centre of the billet, the cavity formation was determined to be caused by plastic cracking under tensile stress. During the piercing process, the strain distribution was U1+W+2U2 along the axial direction and lamellar along the radial direction. The final equivalent strain of the capillary can reach 5-11. The strain rate in the contact area between the blank surface and the discs was 0.71~3.6s_^-1, while that between the surface and the rolls was up to 4.6~26s_^-1, thus contributing to the plastic forming process. The billet temperature in front of the plug was the highest, and the area in contact with the piercing tools decreased slightly. But they were still in the single β phase field. Based on the parameters optimized by the finite element method, the Ti80 alloy seamless tube was successfully pierced through the experimental Diescher mill. The microstructure of the tube was presented as a single Widmanstatten microstructure. Due to the severe deformation, the fine and equiaxed dynamic recrystallization β grains were found from outer surface to the middle layer and to inner surface. The mechanical property test showed that the strength and plasticity of the tube can meet the requirements of the project.