In order to study the effect of plate thickness on residual stress of GH625 superalloy subjected to laser shock peening, on the one hand, laser shock strengthening technology was used to impact 2 mm GH625 plate, and the surface residual stress distribution was obtained by X-ray stress tester; on the other hand, ABAQUS finite element simulation software was used to perform numerical simulation of laser shock GH625 plates with thicknesses of 2 mm, 3 mm, 4 mm, and 5 mm. Through the combined method of experiment and numerical simulation, the Johnson-Cook (J-C) constitutive equation of GH625 high-temperature alloy was optimized. The results indicate that when the strain rate influence factor C is 0.005 21, the simulated residual stress on the surface of laser shocked GH625 is in good agreement with the experimental results. As the thickness of the GH625 plate increases, both the magnitude of compressive residual stress on the surface and the depth of residual stress distribution increase. There is also compressive residual stress on the backside of the plate, which decreases with the increase of plate thickness.