In order to realize high quality and high efficiency welding of large thickness titanium alloy, a flux-cored welding wire was developed by optimizing the synergistic mechanism of metal powder cores, the results show that the liquid molten pool metal has good wetting and spreading flow properties in the process of laser wire-filling welding, and the microstructure evolution of the interlayer region of the welded joint is studied systematically, the stress distribution in the process of laser welding was analyzed by numerical simulation, and the ultra-narrow gap laser welding of 96 mm thick TC4 titanium alloy plate was realized. The average tensile strength of the upper, middle and lower parts of the welded joint is 935 MPa, the average non-proportional tensile strength is 794 MPa, and the elongation rate after fracture is 20% The average value of the impact toughness of the upper, middle and lower welded joints at room temperature is 31 J, and the microstructure and properties of the welded joints are well distributed along the wall thickness, it provides technical support for the long-term stable service of thick-wall titanium alloy welded joint structure under harsh working conditions.