Abstract: In both CO₂ injection and water injection development modes, casing shear damage in mudstone sections will be aggravated. In order to clarify the influence of different injection media on mudstone layer slip, combining the physical and mechanical parameters of reservoir rock obtained from laboratory experiments with the well pattern data of actual blocks, a fluid-structure coupling numerical model of mudstone layer shear slip was established and solved by finite element method. The distribution and variation of pore pressure, reservoir deformation and mudstone slip of different injection media at a certain injection speed during production for three years are analyzed. According to the calculation results, due to the difference in viscosity and density of water and CO₂, the pore pressure around CO₂ injection well is higher than that of water injection well in the early development stage. With the prolongation of development time, the decrease rate of pore pressure of CO₂ injection well is greater than that of water injection well. After three years of production, the overall pore pressure of CO₂ injection oil layer is higher than that of water injection oil layer, which makes the whole CO₂ injection oil layer uniformly lift up, but the height difference of water injection oil layer is larger, resulting in more concentrated deformation of oil layer. The slip amount of mudstone layer is different due to the different deformation amount of oil reservoir, and the slip amount of mudstone layer injected with CO₂ is less than that of cement layer. Based on the analysis of the influence of different injection media on the slip amount of mudstone layer, a reasonable injection scheme is given, which provides theoretical support for preventing casing damage in oilfield.