Abstract: By taking the horizontal-takeoff-horizontal-landing (HTHL) two-stage-to-orbit (TSTO) reusable launch vehicle (RLV) as the research object, a structure weight and size estimation method is proposed in consideration of the engine mode performance and the aircraft resistance characteristics. According to the mission characteristics of the TSTO reusable launch vehicle, the aerodynamic configuration for the first and second stages of the aircraft is designed. With a 2 tons payload and low earth orbit (LEO) as mission requirements, the Mach 6.0 and 30 km altitude are chosen as the separation point, and the vehicle's dimensions, structural weight, and fuel loading are evaluated. The relationship is discussed between the weight and size of vehicle structure and the influence of propellant parameters, engine performance, and flight profile. The results show that the engine efficiency has a significant effect on the size of the aircraft. The liquid fuel has an advantage in terms of takeoff gross weight and is more suitable for TSTO reusable launch vehicle. The flight profile has little effect on the size of the vehicle, and the difficulty of the TSTO reusable launch vehicle conceptual design can be reduced by selecting a reasonable flight profile. The weight and size estimation method and research conclusions constructed in this paper have important reference significance for further development of a TSTO reusable launch vehicle.