• A newly high-performance concrete was prepared by using aeolian sand. • The modified Andreasen & Andersen model was employed to determine the volume fractions of solid powders. • The optimization values of W/C, SP and FA content are 0.19, 1.0 and 25.86 respectively. • The internal pores of developed FAS-HPC are harmless and the pore porosity is 7.3%. • This study further enriches the raw materials for HPC and proposes a fully calculated design method. To solve the shortage issue of high-quality construction aggregates in desert areas and improve the utilization rate of aeolian sand, this study introduces the mix design and characteristics evaluation of high-performance concrete with full aeolian sand (FAS-HPC). The modified Andreasen & Andersen model is employed to determine the volume fractions of solid materials when the mixture system reaches the best packing density. Then the Response Surface Method (RSM) is utilized to conduct the orthogonal design and evaluate the effect of water-cementitious materials (W/C), superplasticizer (SP) and fly ash (FA) content on the flowability, mechanical properties, shrinkage and impermeability of the developed concrete, thus the raw materials proportion of FAS-HPC is optimized. After that, the pore structure and microstructure of the developed concrete are tested and analyzed to verify its durability and compactness. The results show that the volume fractions of AS, silica fume, and cement are determined as 0.482, 0.093, and 0.425 respectively, and the introduction of FA is found to be effective in improving the fluidity and impermeability while reducing the early strength and shrinkage. Under the determined response goals, the optimal values of W/C, SP and FA content are 0.19, 1.0 and 25.86 respectively. While the developed FAS-HPC formed by this ratio has a flowability of 220 mm, 28d flexural strength and compressive strengths of 20.26 MPa and 97.09 MPa respectively, meeting the requirements of HPC. Additionally, the developed FAS-HPC has a porosity of 7.3 % and 76.4 % pores are harmless, which can ensure its superior chloride resistance and durability. This study further enriches the raw materials for HPC and proposes a fully calculated design method, which is of great significance to the sustainable development of HPC.