A high-order sliding mode observer based time-varying sliding mode control strategy is presented to address the robust attitude control problem of uncertain re-entry vehicle. Firstly, a time-varying sliding surface and the corresponding sliding control law are designed respectively, in which the switching gains are obtained through an adaptation scheme. Hence, the requirement of a prior knowledge of the upper bound on the model uncertainty is removed. Further, a high-order sliding mode observer is adopted to get the information of the attitude angle derivatives and estimate the system disturbances as well. Thus, an observer based control scheme is constructed. Finally, a numerical simulation is employed to illustrate the effectiveness of the proposed strategy in improving the attitude control accuracy as well as the system robustness.