In this paper, based on the macroscopic finite element method and the microscopic phase field method, a multi-scale simulation model for laser deposition manufacturing (LDM) of TC4 titanium alloy gradient structure was constructed. The model successfully predicted the microstructure evolution of TC4 gradient structures obtained with different deposition layouts and process parameters. The results show that in the gradient structure of large-spot high-energy density deposition followed by small-spot low-energy density deposition, the grains transit from coarse columnar crystals to fine columnar crystals. The formation mechanism of the gradient structure includes the generation of the coarse columnar crystal interface, the nucleation of the fine columnar crystal and the continuous epitaxial growth and competitive growth of the fine columnar crystal. In the sample deposited along parallel directions, small-size grains grow on the top of largesize grains. In the sample deposited along vertical directions, small-size grains nucleate and grow vertically in a T-shape adjacent to the large-size grains. According to the simulated process, TC4 gradient structures were fabricated by LDM and the experimental observations match the simulation outcomes.