An agricultural vertical take-off and landing (VTOL) tail-sitter UAV with symmetrical winglets and wings was designed. The main parameters of the tai-sitter, wingspan, sweep angle, winglet height and winglet thickness were investigated to optimize the structure design. Central composite design (CCD) was employed to construct 25 sample points. Numerical simulation of lift drag ratio and drag were carried out with ANSYS CFX. The response surface models (RSM) of UAV structure parameters with lift drag ratio and drag were established by Design-Expert software. The lift drag ratio was increased with the increase of wing length and height of winglet. The lift drag ratio was decreased with the increase of wing thickness at attack angle of 4°~8°, and with the decrease of wing thickness at attack angle of 10°~12°. The impact of sweep angle and wing height on the lift drag ratio was small. The drag was increased with the increase of wing length and thickness of wing, and decreased with the increase of winglet height. The drag was increased firstly with the increase of sweep angle and then decreased. The multiobjective genetic algorithm was used to optimize the structural parameters, with maximum lift drag ratio and minimum drag as optimal objects. The optimal structural parameters were wingspan of 1123mm, sweep angle of 34°, wing height of 39mm, and wing thickness of 3mm. Compared with the original configuration, the average lift drag ratio was improved by 12.4%, while the average drag was reduced by 5.3%. The response surface model was validated by wind tunnel test. The numerical simulation error of lift drag ratio and drag was less than 8.0%, and the error of response surface model was less than 3%. It was shown that the response surface model had high accuracy and good versatility, and it can be used in the optimization design of vertical takeoff and landing of tailstock UAV. The results were of great significance for the design of tailsitter UAV.