The hydraulic phosphogypsum cementing material system studied in this paper is composed of 80% (mass fraction) phosphogypsum and a small amount of auxiliary cementing materials such as slag, cement, metacaolin, fly ash and silica fume. Mechanical properties test and molecular dynamics (MD) simulation are used to provide a basis for the composition design of high content phosphogypsum system, and then the strength shrinkage of the system is adjusted. The results show that when the content of phosphogypsum is fixed, the n(CaO)/n(SiO2+Al2O3) molar ratio of the supplementary cementitious material (SCM) is close to 1, and the mechanical properties of the sample are the best. The results of molecular dynamics simulation on the atomic surface area and pore structure distribution of the model are consistent with the mechanical properties. The smaller the pore structure, the higher the compressive strength. On the atomic scale, O, Ca, Al and S atoms show high diffusion ability in molecular dynamics simulations with the molar ratio of n(CaO)/n(SiO2+Al2O3) close to 1, which can give full play to alkali and sulfate excitation effects, and at the same time, increase the bond length of OO, Al—O and Si—O, resulting in unstable hydrolysis and promote the formation of calcium vanadite as a hydration product. Finally, by adjusting the types of auxiliary cementing materials, adding metakaolin, wollastonite and fly ash into phosphogypsum-slag-cement system, the problem of strength shrinkage at 90 d age is improved. It is of great significance to design and use phosphogypsum based on chemical composition and obtain better cementing materials.