Abstract: On the basis of the statistical analysis of the actual seismic acceleration records, this paper gives the parameters describing the non-stationary of earthquake ground motion and their value ranges. And the design of experiments (DOE) method is introduced to establish suitable algorithm to analyze the influence of the change in the non-stationary characteristic parameter of ground motion on the structure responses. Furthermore, an approximate quantitative relationship between the non-stationary characteristic parameters of the earthquake ground motion and the structural responses is established by combining with approximate technology. The results show that: ① The DOE method presented in this paper is suitable for the analyses of non-stationary characteristic parameters of ground motion intensity, and satisfied results can be obtained based on the less amount of calculation. ② Variance analysis of characteristic parameters based on DOE method shows that the steady-state duration of ground motion has significant influence on the seismic response of the structure; for structures with shorter period, the interaction between characteristic parame-ters has a significant impact on seismic response of structures, but when the period is greater than 1 s, its influence gradually decreases. ③ The approximate quantitative relationship established in this paper can better reflect the relationship between different characteristic parameters and different structural dynamic response, providing the theory basis for engineering practice to setting up reasonable seismic characteristic parameters based on the structural characteristics and synthetize or select earthquake acceleration time history.