In order to quantitatively evaluate the influence of random spatial distribution of rock blocks on the stability of soil-rock mixture slopes, the random rock block model and equivalent strength parameter reliability model were adopted to evaluate the stability of a soil-rock mixture slope. At first, the random rock block model was used to generate a soil-rock mixture slope with random spatial distribution of rock blocks. Then, the strength reduction method of finite element analysis was used to evaluate the influence of the random distribution of rock blocks on the stability of the slope. At the same time, the uncertainty and risk analysis of the soil-rock mixture slope was carried out using response surface method, considering the soil-rock mixture with the random distribution of rock blocks was equivalent to a homogeneous material with the values of its shear strength parameters falling in a certain range. The results show that the random block model can reveal the phenomena of “bypassing the blocks” and “splitting” of multiple plastic shear zones when encountering random blocks, and different spatial distribution of rock blocks have different influence on the plastic shear zones. What’s more, the equivalent strength parameter reliability model is suitable for the engineering quantitative evaluation of the stability of soil-rock mixture slopes.