The prediction of the unit grouting quantity is one of the key points in the design and construction of karst curtain grouting. Because of the concealment and complexity of the karst curtain grouting project, there is no reliable solution to this problem. In this paper, based on the calculation method of water permeability in water-pressure test in grouting engineering, Poiseuille flow equation in fluid mechanics, and cubic law, the relationship between the unit grouting quantity and the water permeability of rock strata in karst curtain grouting is studied. It is found that there is a nonlinear positive correlation between the unit grouting quantity and the water permeability of rock strata in karst curtain grouting, which is in the form of power function. At the same time, the comprehensive coefficient of karst curtain grouting ( K ) is introduced to describe the quantitative relationship between the unit grouting quantity and the water permeability of rock strata. K is comprehensively characterized by three controlling factors, namely, the characteristics of slurry fluid, the characteristics of grouted rock strata, and the technical factors of grouting in karst curtain grouting. Based on this theoretical relationship, a method for predicting the unit grouting quantity in karst curtain grouting by the water permeability of rock strata is proposed in this paper. Finally, based on the typical example of karst curtain grouting project, through the field grouting test and nonlinear function fitting, the comprehensive coefficient of karst curtain grouting ( K ) is 24.37 in the area of strong karst development, and it is 16.51 in the area of weak karst development. The proposed method is applied to the prediction of the unit grouting quantity in the main project of karst curtain grouting, and the results verify the rationality and applicability of the method. This study has a certain reference value and guiding role in the design, construction, and theoretical research of karst curtain grouting.