Abstract: Hot extrusion is one of the most important manufacturing methods for titanium alloy tubes, and the extrusion process parameters are critical to the tube quality. In this study, finite element simulation and response surface methodology have been employed to investigate the hot extrusion process. Response surface models have been established for both the billet transfer process after heating and the subsequent extrusion process. The effects of billet heating temperature, transfer time, extrusion speed, and die angle on the thermo-mechanical coupling behavior during hot extrusion have been analyzed. Optimization of the extrusion process parameters has been conducted with the maximum temperature and maximum extrusion force as objectives. The results show that when the heating temperature is 1 122.55 ℃, the extrusion speed is 100 mm/s, and the die angle is 90°, the maximum temperature during extrusion reaches 1 145.6 ℃ and the maximum extrusion force is minimized. The error between the predicted and actual values is less than 1%. Among all parameters, the heating temperature has the most significant impact on both the maximum temperature and maximum extrusion force during the process.