This paper deals with an autonomous flight guidance and control algorithm design for TR301 tilt-rotor airplane under development by Korea Aerospace Research Institute for simulation purpose. The objective of this study is to design autonomous flight algorithm in which the tilt-rotor airplane should follow the given waypoints precisely. The approach to this objective in this study is that, first of all, model-based inversion is applied to the highly nonlinear tilt-rotor dynamics, where the tilt-rotor airplane is assumed to fly at helicopter flight mode(nacelle angle=0 deg), and then the control algorithm, based on classical control, is designed to satisfy overall system stabilization and precise waypoint following performance. Especially, model uncertainties due to the tiltrotor model itself and inversion process are adaptively compensated in a simple neural network(Sigma-Phi NN) for performance robustness. The designed algorithm is evaluated in the tilt-rotor nonlinear airplane in helicopter flight mode to analyze the following performance for given waypoints. The simulation results show that the waypoint following responses for this algorithm are satisfactory, and control input responses are within control limits without saturation.