More plastic deformation will concentrate on the column ends due to the coupling effects of bi-directional horizontal seismic action, and the plastic hinges distributions of spatial frame under bi directional horizontal seismic action is obviously worse than that of the corresponding plane frame. Regular reinforced concrete 3D spatial frame of the second seismic grade at 8-earthquakeintensity 0.2g-region was designed strictly according to the Chinese code, and seven spatial frame examples were obtained by the combination of varying strong column-weak beam measure in the upper stories with moment amplification factor at bottom sections of ground floor column. Based on the OpenSees framework, the flexibility method based fiber model was adopted to simulate the nonlinear responses of columns under biaxial bending and varying axial force effectively. The nonlinear response analyses of the seven frames under rare earthquake excitation were carried out. The results showed that under bi-directional horizontal seismic action, the strong column-weak beam measure of the second seismic grade at 8-earthquake intensity of Chinese code is evidently weak; the spatial frame develops column hinges mechanism with story side sway mechanism occurs at some floors. When strong column-weak beam measure in the upper stories is based on the actual reinforcement area of beam ends, namely ∑Mbua,the controlling effects on plastic hinge mechanism are acceptable, but excessive nonlinear damage focuses on the bottom sections of ground floor columns. When the moment amplification factor at bottom sections of ground floor columns increase to 1.8, and strong column weak beam measure in the upper stories remains to be ∑Mc=1.25∑Mb,a relatively optimal controlling effect on plastic hinge mechanism could be obtained.