In order to solve the problem of the analysis of seismic response for nonlinear pile-soil-structure interaction system with uncertain parameters subjected to stochastic external excitation, a simple and practical method was proposed in this paper, and the corresponding plug-in program was developed on the platform of universal software ANSYS. Firstly, the stochastic vibration analysis was converted into the definite harmonic vibration analysis accurately by means of the pseudo-excitation method. Secondly, perturbation theory of small parameter was introduced to consider the uncertain material parameters and direct interpolation equivalent linearization model was used to simulate the nonlinearity of material. Finally, the effects of the variability of shear modulus, damping ratio, density and Poisson’s ratio on the stochastic seismic response of the pile-soil-structure interaction system are studied. The results show that the variability coefficients of the response have the same magnitude as the input material parameters and the influence of the variability of material parameters on the response magnitude can’t be ignored.