Thin-walled structures of future hypersonic flight vehicles will encounter complex loadings and exhibit obvious nonlinear responses. The thermal loads from high speed flow or engine jet flow can cause thermal buckling of thin-walled structures, such as Thermal Protection System (TPS). If the structures are loaded with intense acoustic loads simultaneously, large deflection nonlinear response, including snap-through, can be induced. Snap-through will give rise to large amplitude stress cycles and non-zero mean stress, which can lessen the fatigue life markedly. Starting from Hooker’s Law with thermal components, the large deflection governing equations of motion for simply-supported plate under thermo-acoustic loadings are derived. The partial differential equation (PDE) of motion which is difficult to solve is then transformed with Galerkin’s method to the system of ordinary differential equations (ODE) under modal coordinates. The displacement responses under different combinations of temperature increments and sound pressure levels are calculated by employing Runge-Kutta method. Typical thermo-acoustic responses are predicted: 1) random vibration around pre-buckled equilibrium position, 2) persistent snap-through between post-buckled positions, 3) intermittent snap-through, 4) vibration around one of the two post-buckled positions. By dividing the restoring force term in the equation into linear term and nonlinear one, the evolutions of each term are obtained to illustrate the mechanism of thermo-acoustic response and the contributions of each force, including shear force, thermal force and membrane force. Thus a further insight into thermo-acoustic response has been achieved.