The majority of earthquakes in Chinese mainland focused on the Tibetan Plateau and its surroundings, where not only associated with the complex tectonic deformation history, but also have a significant gravity anomaly characteristic. In this paper, we employed the EGM2008 gravity model, and computed the regional Bouguer and Airy isostasy gravity anomaly in the Tibetan Plateau and its surroundings. On the theory of combined isostasy model, we refer to the Moho depth from the Crust1.0 model, and inverse the crustal residual density distribution, which can be used to study the lateral density difference. At last, we compared with the lithospheric effective elastic thickness derived from the elastic plate model. The results show that the mechanical property and average density have a significant difference between the crust blocks of the Tibetan Plateau and surroundings, which provided a geodynamic background for the great earthquake preparation. The results could also provide a reference for estimating potential earthquake hazard locations.