To prevent tunnel in waterrich fault zone from water and mud inrush disaster, the critical safety thickness of tunnel should be determined. A model considering the mechanics and seepage parameters of surrounding rock, tunnel and fault zone parameters is established using the methods of numerical simulation and engineering verification. The multilevel numerical tests of various factors in standard working conditions are performed to analyze the influence of various factors on the critical safety thickness. Multivariate linear regression analysis is used to establish a multifactor prediction formula, and the formula is verified through six engineering examples. The research results show the following. (1) The surrounding rock parameters of waterrich fault zone such as Poisson′s ratio, permeability coefficient, and void ratio and the Poisson′s ratio of ordinary surrounding rock have little inference on the critical safe thickness. (2) The factors such as water pressure, buried depth, thickness of fault zone, tunnel diameter, elastic modulus of the surrounding rock of the fault zone, and ordinary surrounding rock parameters (elastic modulus and void ratio) are positively related to the critical safety thickness of water inrush, whereas the strike and dip of the fault zone, ordinary surrounding rock parameters (severity, internal friction angle, cohesion, and porosity ratio), and the surrounding rock parameters of the fault zone (severity, internal friction angle, and cohesion) are negatively related to the critical safety thickness. (3) The calculation results of prediction formula are more consistent with the results of numerical simulation and the actual project, indicating its effectiveness and guidance value to the project.