We have examined shear-wave splitting in teleseismic waves (SKS) recorded on 20 seismographs deployed on a profile that followed the Southern Tibet highway during the 1992 Sino-French seismic experiment. The “cross-correlation” method is applied to derive splitting parameters. The most striking feature is the abrupt variation in splitting orientation across ITS. North of ITS, 12 stations have an average N70°E orientation of the fast wave, with a delay between the fast and slow waves of up to 1 second. On the contrary, 7 stations located to the south of ITS show an N25°W orientation and a smaller magnitude. We compare the observations with surface geological features and discuss the source of anisotropy and its constraints on the deformation model of the Tibetan Plateau. Our studies suggest that the anisotropy may be generated by the high strain induced by the underthrusting of the India lithosphere in the south of ITS. North of ITS, anisotropy may relate to ductile deformation and flow in the upper mantle. Analysis of the anisotropy pattern with the deformation models of the Tibetan Plateau suggests that both internal ductile deformation and continental northeastward extrusion contribute to crustal shortening and uplift of the Tibetan Plateau.