In order to overcome the influence of internal and external disturbances caused by rotor tilt motion and gust disturbance on the full flight mode control of a tilt-rotor unmanned aerial vehicle (UAV), a design method using fuzzy backstepping control based on an extended-state observer (FBS-ESO) is proposed. In this paper, fuzzy control is used to tune the parameters of the backstepping control law online, and the extended-state observer estimates the total disturbance of the controlled system to improve the controller’s robustness and anti-disturbance capability. This paper designs the attitude control system of a tilt-rotor UAV based on an FBS-ESO controller. The control performance of the FBS-ESO controller is tested in a hardware-in-loop simulation of the attitude control system. The simulation results show that changing the rotor tilt angle will destroy the stability of the traditional backstepping controller and active disturbance rejection controller (ADRC). In contrast, the FBS-ESO controller maintains good control performance. In addition, the performance of the FBS-ESO controller is not be significantly affected by adding external gust disturbance or changing the UAV parameters in the simulation. These disturbances significantly impact the traditional backstepping controller and ADRC. Therefore, the FBS-ESO controller has better anti-disturbance capabilities and robustness, as well as higher attitude control accuracy.