By using two seismic profiles along 30°N and 31°N in western Sichuan, China deployed by Institute of Geology, China Earthquake Administration, Virtual Deep Seismic Sounding (VDSS) method was applied to study the crustal structure in Sichuan-Yunnan region. The results show distinct Moho depth from VDSS at Sichuan-yunnan Rhombic Block, Songpan-Garze block and Yangzte block. 1) The Moho depth from VDSS in Sichuan basin is about 40 km, 2) Moho depth from VDSS beneath Sichuan-yunnan Rhombic Block is about 45-50 km, 3) Moho depth from VDSS beneath Songpan-Garze block is about 30-40 km. The Moho depth from VDSS in Sichuan basin is consistent with that predicted from Airy isostasy, while the Moho depth from VDSS at Chuan-Dian Fragment and Songpan-Garze block is clearly shallower than the Moho depth from previous receiver function studies, and those predicted from the Airy isostasy as well. These results may suggest that the crustal structure beneath Sichuan basin is relatively simple while there are complex crustal structure beneath Sichuan-yunnan Rhombic Block and Songpan-Garze block. In addition, the Moho depth from VDSS are clearly reduced at Xianshuihe fault and Anninghe fault, which might reflect mantle upwelling along the fault zones. The results provide new constrains to understand the deformation mechanism at southeastern margin of Tibetan Plateau.