The room temperature spalling of oxide scale is an important phenomenon for the application of high temperature alloys or coatings. In this study, the mechanism of the time-dependent spalling behavior of the thermally grown oxide (TGO) formed on a Pt-diffused bond coat was investigated. To detect the interfacial deformation at room temperature, the surface roughness of the TGO was measured in situ as function of time immediately after cooling, which reflected the change of interfacial morphology. Finite element analysis was employed to simulate the deformation and crack nucleation at the interface. It was proposed that the room temperature plastic deformation could occur at the TGO/bond coat interface, leading to the crack nucleation. Furthermore, the effect of the interface geometry on the crack length was also studied. It was inferred that the time-dependent spalling behavior of the TGO might be associated with the room temperature deformation of the interface.