Abstract: This paper investigates the internal and external quality, as well as mechanical properties, of laser spot welding of TC4 titanium alloy under different parameters of defocusing amount, welding power, and welding speed. Field emission scanning electron microscopy and optical microscopy were employed to observe and analyze the internal and external quality of the weld spots, and shear strength tests were conducted to analyze the influence of laser power on shear strength. The shear strength differences between laser spot welding and resistance spot welding were also compared. The results show that the defocusing amount can effectively increase the penetration depth and improve the nugget diameter of the weld spots. Higher laser power leads to a larger nugget diameter of the weld spots. An increase in welding speed can improve the surface quality of the weld spots and reduce surface depressions. There is a positive correlation between the shear strength of the laser spot welding specimens and the nugget diameter. Compared with resistance spot welding, the shear strength of laser spot welding is lower.