The study of dynamic response of rock slope with soft layer is always an important subject in slope stability. In order to further explore the feature of weak layer to the influence of the dynamic response of rock slope in the engineering background of Daguangbao Slope, slope model is established by means of FLAC3D and design scheme using the DOE methods. The effects of Angle, Thickness, Elastic-Modulus, Tensile-Strength, and Poisson'sRatio of the soft layer on the PGA amplification of slope top are investigated, as well as their relevance. ANOVA method is used to analyze the data, and it is concluded that the Angle, Thickness and Elastic-Modulus of soft layer have significant influence on the amplification effect of slope, and the significance degree is Angle > Thickness > Elastic-Modulus. In addition, within a certain range, the slope acceleration amplification coefficient increases as the inclination angle increases and reduces as the thickness and elastic modulus increase. Simultaneously, the interaction between dip Angle and Thickness, Elastic-Modulus, and Tensile-Strength influences the amplification impact of rock slope to a degree. When the inclination Angle is small, the PGA amplification coefficient decreases with the increase of Thickness, Elastic-Modulus and Tensile-Strength. When the Elastic-Modulus is large, the amplification coefficient decreases with the increase of Tensile-Strength.