Abstract: α high-strength gypsum (α-HH) composites are an important way to realize the high-value and large-scale utilization of phosphogypsum. However, at present, α-HH products generally have problems such as poor water resistance and low compatibility between modified powder and polymer. Therefore, a hydrophobic modification technology was proposed to improve the interfacial compatibility between α-HH and polymers. In this study, Dodecylamine (DDA) was used to hydrophobly modify α-HH, and the effects of modifier dosage, modification time and system pH on the hydrophobic properties of α-HH were systematically investigated, and the experimental conditions were optimized by response surface method, and the modified α-HH powder (M-α-HH) was finally obtained. In addition, M-α-HH/polyethylene (PE) composites were prepared by compounding and extrusion process. The experimental results showed that when the mass ratio of α-HH to DDA was 5∶2, the modification time was 60 min, and the pH of the system was 10, the hydrophobicity of the resulting M-α-HH was optimal, and its contact angle with water reached 140°. Further studies show that when the incorporation amount of M-α-HH is 30%, the flexural strength and tensile strength of M-α-HH/PE composites reach 73.40 MPa and 35.43 MPa, respectively, which are 21.66% and 66.18% higher than those of pure PE, showing excellent interfacial compatibility and mechanical properties. This study not only provides a new idea for the high-value utilization of phosphogypsum, but also provides an important reference for the development of green and low-carbon materials and the functional utilization of industrial solid waste.