The work aims to establish a fatigue life prediction model for titanium alloy and verify feasibility of this model in predicting titanium alloy fatigue life after barrel finishing by virtue of experimental study. Influencing law of roughness and residual stress on TC4 titanium alloy fatigue life was studied by virtue of finite element simulation and multivariate regression orthogonal experiment. Relation equation among fatigue life, roughness and residual stress was simulated, correctness of the simulation results and equation were further validated by experiments. After the barrel finishing, the roughness of TC4 board changed from Rz=3.16 to Rz=1.69. The initial residual tensile stress turns into compressive residual stress from 50 MPa to ?228 MPa. The fatigue life increases from 28,083 to 39,510 times and has increased by 40.6%. Compared with the results of simulation, the error is about 5%, testifying feasibility of simulation results. Therefore, a fatigue life prediction model is provided for titanium alloys subject to barrel finishing.