The soil -structure relative stiffness is a key factor affecting the seismic response of underground structures. It is of great significance to study the soil -structure relative stiffness for the soil -structure interaction and the seismic disaster reduction of subway stations. In this paper, the dynamic shear modulus ratio and damping ratio of an inhomogeneous soft soil site under different buried depths which were obtained by a one-dimensional equivalent linearization site response analysis were used as the input parameters in a 2D finite element model. A visco-elasto-plastic constitutive model based on the Mohr -Coulomb shear failure criterion combined with stiffness degradation was used to describe the plastic behavior of soil. The damage plasticity model was used to simulate the plastic behavior of concrete. The horizontal and vertical relative stiffness ratios of soil and structure were defined to study the influence of relative stiffness on the seismic response of subway stations in inhomogeneous soft soil. It is found that the compression damage to the middle columns of a subway station with a higher relative stiffness ratio is more serious while the tensile damage is slighter under the same earthquake motion. The relative stiffness has a significant influence on ground surface deformation, ground acceleration, and station structure deformation. However, the effect of the relative stiffness on the deformation of the bottom slab of the subway station is small. The research results can provide a reference for seismic fortification of subway stations in the soft soil area.