Aiming at the fiber laser welding of 1.2 mm thick TC4 titanium alloy sheet, the effects of different welding parameters on the mechanical properties of the weld were studied by orthogonal test. The optimum process parameters of TC4 laser welding were obtained. The differences in microstructure and properties of weld samples and base metal samples under optimal welding parameters were compared by optical microscopy, microhardness, tensile test and bending test. The results show that the laser power has a great influence on the tensile strength, while the defocusing and the welding speed have the same level of influence. When the welding specification is reasonable, the tensile strength of the joint reaches more than 93% of the base metal, and the elongation is more than 83% of the base metal. The fracture site mainly appears in the base metal area, the fracture is ductile fracture, and the dimple morphology is visible.