In order to realize the resource utilization of industrial by-product phosphogypsum, based on the central composite design method in response surface method, sulfoaluminate cement (SAC) and protein retarder (SC) content were selected as variables to optimize the performance of hemihydrate phosphogypsum cementitious material (HPCM) and prepare high performance HPCM. The response surface curves of relationship between the variables and 1 d compressive strength, dry compressive strength, initial setting time and final setting time were obtained through data processing, and the corresponding response surface models were established. The results show that the optimal mass content of SAC and SC is 20.48% and 0.12%, respectively. The dry compressive strength of HPCM is 23.1 MPa and the initial setting time is 38 min. The mechanical properties and working properties of HPCM are good. Based on the analysis of the hydration process and the composition of hydration products, it is mainly that the change of mineral phase leads to the generation of new hydration products, which improves the microstructure of the system, so as to optimize the performance.