A finite-time disturbance observer-based nonsingular terminal sliding mode control strategy is proposed for flexible hypersonic vehicle (FHV) with mismatched uncertainties. First of all, by considering the effects of flexible modes as uncertainties, the control-oriented model, which is convenient for controller design, is obtained by simplification of the FHV model. Then, the lumped uncertainties are estimated by finite-time disturbance observer. Afterwards, a novel nonsingular terminal sliding surface containing the disturbance estimations is designed, which can transform the high-order mismatched uncertainties into first-order matched uncertainties. Then the controller is developed. The stability of the closed-loop system is guaranteed by Lyapunov theory. Simulation results show that the proposed controller is effective in suppressing the mismatched uncertainties and has achieved stable tracking of velocity and altitude