Laser-MIG hybrid welding (LMHW) has not been extensively applied in welding of plate-pipe dissimilar steel with thick-walled because of the complex welding process requirements. In this study, numerical simulation and experimental studies of LMHW with different parameters of 25CrMo4 steel and 33MnCrB5-2 steel are presented. A 3D finite element model with coupled thermal-structural is established for analyzing the effects of welding parameters on the posted-weld thermal field, residual stress, and deformation distribution by using combined ellipsoid-Gaussian heat source model. Comparison of the calculated and experimental results suggested that the LMHW process is characterized well by the combined heat source model. Additionally, the inter-layer cooling time is determined by the amount of heat input, which also affects the magnitude and distribution of residual stress. Residual stress and deformation are controlled within the adaptable range. But, the component cannot be penetrated when laser power of backing weld P is 6000 W and welding current I is 282 A.