We combine the latest horizontal and vertical GPS velocity fields in the southeastern margin of Qinghai-Xizang plateau, based on the strain solving method of spherical wavelet multi-scale analysis, consider the weight relationship between regional seismic moment and strain distribution, obtain the three-dimensional crustal strain characteristics of the southeastern margin of Qinghai-Xizang plateau, and analyze the relationship between regional deformation characteristics and seismicity. The results show that: 1) There is a consistency between surface strain and vertical strain in the study area. The high surface strain and low vertical strain are mainly concentrated in the central Qinghai-Xizang plateau and northern Jinshajiang regions, while the low surface strain and high vertical strain are mainly concentrated in the Eastern Himalayan Syntaxis and Longmenshan regions. The spatial inverse distribution relationship between surface strain and vertical strain shows that the horizontal velocity and vertical velocity obtained by GPS observation in this region are coupled, which indicates that vertical motion is also an indispensable consideration for the study of crustal deformation and seismic risk in this region. There is a good agreement between surface strain and vertical strain in terms of magnitude, which further indicates that the crustal deformation in this region can be approximated as a continuous and homogeneous elastic behavior. 2) There is a consistency between the type of strain rate and focal mechanism solution. The strain types obtained from GPS data in the southeastern margin of Qinghai-Xizang plateau can be well matched with the focal mechanism solution in this region. The source mechanism of normal fault is mainly distributed in Jinshajiang region, thrust fault is mainly concentrated in Longmenshan and Eastern Himalayan Syntaxis regions, and strike-slip fault is mainly distributed near the fault zone with significant strike-slip shear such as Xianshuihe-Xiaojiang fault, indicating that the strain characteristics obtained from GPS observation can better describe the tectonic stress field characteristics in this region. Combined with the spatial distribution characteristics of stress and strain in this region and seismic tomography results, we believe that the Longmenshan fault and Eastern Himalayan Syntaxis are in compressive strain state.