This paper aimed at evaluating the influence of different site conditions on the impact response of the structure of nuclear power plants (NPPs) against a large commercial aircraft. The lumped parameter site dynamic model recommended by the code of ASCE 4-98 was used to consider the different homogeneous sites. With respect to the excellent impact resistant performance of steel-plate concrete (SC) structure, the full SC containment is selected as the research object. The impact analysis of the full SC containment against a large commercial aircraft under different site conditions was carried out, based on the force time-history analysis method. The numerical results in terms of the displacement, plastic strain, local concrete damage, and different values of energy were evaluated. The results showed that: (1) For the relatively thin full SC containment, the impact response under the fixed boundary is the largest, while that calculated by other, different sites varies greatly, and there is no consistent rule, the boundary condition which is assumed to be fixed is relatively conservative. (2) For the thicker full SC containment, the displacement response decreased with the increasing of the site shear wave velocity, which is the smallest when the fixed boundary is considered. When the shear wave velocity of the site is large enough, its boundary condition which is assumed to be the fixed constraint is reasonable. (3) For the relatively thin full SC containment, the site damping effect has a significant effect on the structural impact response. Nevertheless, the impact response of the thicker containment is slightly influenced by the site damping effect. (4) For the impact analysis of the structures of NPPs against a large commercial aircraft, it is suggested that both the specific site condition and fixed boundary should be considered.