To meet the design requirements of long-endurance hydrogen energy hybrid powered Unmanned Aerial Vehicle, the combined MATLAB and XFOIL optimization methods, based on the optimized airfoil, were used to optimize the design of the airfoil of HM114. Two aerodynamic layouts for straight wing and elliptical wing (HY1) were designed. Computational fluid dynamics was adopted to analyze the aerodynamic performance of the two layouts. The results show that the lift coefficient of the optimized airfoil is increased by 12.38%, and the lift-drag ratio is increased by 14.03%; the two layouts achieve the maximum lift-drag ratio when the angle of attack is α=4°, while the stall angle of attack is α=12°, the HY1 layout’s smaller pressure difference can contribute more lift to UAV; the HY1 layout has better stall performance when the pressure boundary of the wing surface is behind; both schemes satisfy the longitudinal static stability, but the HY1 layout has better stability. The results of aerodynamic optimization and flow field characteristic analysis in this paper can provide a reference for the aerodynamic layout design of hydrogen energy long-endurance fixed-wing aircraft.