In this paper, the shape evolution and thermal stability of Ag nanoparticles (NPs) on spherical SiO 2 substrates were investigated by means of in situ transmission electron microscopy (TEM) imaging and differential scanning calorimetry (DSC). The initial Ag NPs at room temperature were semispherical-like, with an average size of 9nm in half-height width, well-dispersed on spherical SiO 2 substrates. No obvious shape change was observed when the semispherical NPs of Ag were heated at temperature lower than 550°C. The shape of the semispherical Ag NPs changed gradually into a spherical one in the temperature range of 550–700°C, where surface diffusion and surface premelting took place. When the heating temperature was increased up to 750°C, the spherical Ag NPs were found to desquamate from the substrates due to the decreases of the contact area and the binding force between Ag NPs and SiO 2 substrates. A possible mechanism for the desquamation of Ag NPs from the SiO 2 sphere surface is proposed according to the results of in situ TEM observation and DSC analysis.