Seepage failure in the form of piping can strongly influence the stability of block-in-matrix-soils (bimsoils), as well as weaken and affect the performance of bimsoil structures. The multiple-factor evaluation and optimization play a crucial role in controlling the seepage failure in bimsoil. The aim of this study is to improve the ability to control the piping seepage failure in bimsoil. In this work, the response surface method (RSM) was employed to evaluate and optimize the multiple piping parameters to maximize the critical hydraulic gradient (CHG), in combination with experimental modeling based on a self-developed servo-controlled flow-erosion-stress coupled testing system. All of the studied specimens with rock block percentage (RBP) of 30%, 50%, and 70% were produced as a cylindrical shape (50 mm diameter and 100 mm height) by compaction tests. Four uncertain parameters, such as RBP, soil matrix density, confining pressure, and block morphology were used to fit an optimal response of the CHG. The sensitivity analysis reveals the influential order of the studied factors to CHG. It is found that RBP is the most sensitive factor, the CHG decreases with the increase of RBP, and CHG increases with the increase of confining pressure, soil matrix density, and block angularity.