In this study, the durability of phosphogypsum (PG)-based cemented backfill was investigated by drying-wetting cycles to explore deterioration of its strength and the release of impurities. The leachates in this test were composed of deionized water, 5% Na2SO4 solution, 5% NaCl solution, and a range of sulfuric acid solutions with pH values of 1.5, 3, and 5. After drying-wetting cycles, unconfined compressive strength (UCS), visual deterioration, porosity, microstructure and concentrations of phosphate and fluoride in the leachates were measured. The results showed that both saline and acidic solutions could lead to strength reduction of PG-based cemented backfill under different deterioration mechanisms. The mechanical damage of salinity was caused by micro-cracking and degradation of C–S–H. However, the H+ broke the backfill by dissolving hydration products, leaving the conjunctures between PG particles weakened. Furthermore, the environmental impact was investigated by measuring the concentration of phosphate and fluoride in the leachates. In acidic solutions, the release of phosphate and fluoride was greatly enhanced by H+. Compared to the great strength deterioration in saline leachates, the concentration of phosphate and fluoride were similar to that of deionized water, indicating that saline solutions had little impact on the release of hazardous impurities.