Abstract: This article uses RSM (Response Surface Methodology) to optimize the parameters of ultrasonic-assisted laser welding of titanium and polyethylene terephthalate (PET), and mainly studies the influence of laser power, ultrasonic amplitude and ultrasonic load time on joint strength, bubble defect and the thickness of welding transition layer. Using XPS (X-ray photoelectron spectroscopy) to analyze the effect of ultrasonic load time and amplitude on the formation of beneficial chemical bonds at the interface. The results show that the law of the influence of laser power, ultrasonic amplitude and ultrasonic load time on welding strength are the same, that is, after reaching the maximum value, the welding strength decreases as the parameter value increases. When the laser power is 60W, the increase of the ultrasonic load time or amplitude will promote the formation of Ti-C bonds and increase the thickness of the welding transition layer. Experiments also show that when the laser power is less than 65W, the introduction of ultrasonic vibration can cause bubbles to flow and reduce bubble defects effectively.