Aiming at solving the control problem caused by the large-scale change of the Hypersonic Glide Vehicle (HGV) parameters, this paper proposes a design method of backstepping variable structure attitude controller based on Nonlinear Extended State Observer (NESO), with the characteristics of HGV model and the idea of uncertainty estimation and compensation associated. Firstly, the design of the second-order NESO is studied. Due to the large number of NESO parameters, a systematic method for determining the second-order NESO parameters is given in this paper, and the stability of the observer is proved completely using the piecewise Lyapunov analysis. Then, the NESO-assisted backstepping variable structure attitude controller employs the reduced-order modeling idea to decompose the whole system design problem into two first-order subsystem design problem, and classifies the nonlinear dynamic changes caused by the large-scale changes of the aircraft parameters into the aggregated uncertain terms of the two subsystems. The simulation results show that the backstepping attitude controller based on NESO can realize the stable and accurate tracking of the flight attitude when the aircraft parameters change in a large range.