Phosphosilicate glasses are widely used in optical fiber, biological materials and other fields because of their excellent optical properties and biological activity. The influence of Li2O content on the microstructure and diffusion properties of Na2O-Al2O3-SiO2-P2O5 glass was investigated via molecular dynamics simulation, and the relationship among the microstructure, Vickers hardness and diffusion coefficient was analyzed. The results show that the degree of phosphorus network polymerization (QP) increases with the substitution of Li2O for Na2O, and the hardness increases with the increase of QP. The self-diffusion of Li+ ions is greater than that of Na+ ions, indicating that Li+ ions are easier to diffuse rather than Na+ ions. The potential barrier of Li+ ions decreases with the increase of Li2O. Li2O is beneficial to the substitution of Na2O for the diffusion of Li+ ions.