The Junchang tunnel is a part of a major project in the Censhui highway in Guangxi province, China. The weathered granite part of the tunnel is approximately 180 m long with two lines and four lanes. Numerous water and mud inrush disasters frequently occurred in the weathered granite area, leading to serious economic loss and challenge to the constructors. Therefore, continuous grouting was carried out for the entire weathered part of the tunnel. This paper describes its curtain grouting for disasters prevention. Detailed discussion is presented on the safety thickness after grouting and the challenges encountered under different hydraulic-geological conditions. Specifically, a water and mud inrush model for the nonlinear flow and mass transfer behavior of weathered granite was used to evaluate the safety thickness in this project. Then, field studies with twenty-five grouting cycles and excavations were conducted to investigate the effective safety thickness. Negative correlation was observed between the safety thickness and the rock classification index [BQ]. Numerical simulation and field tests demonstrated that the thickness l should be larger than 3 m, and, in most cases, 5 m was sufficient when [BQ] < 72.5. When [BQ] ≥ 72.5, l should be between 1.5 m and 3 m. Based on the field data, an empirical formula was developed to determine the thickness under different values of [BQ]. The research findings serve as an important reference for future projects in similar stratum.