Background and aims <p>Phosphogypsum (PG) accumulation, soil acidification, and cadmium (Cd) pollution threaten agricultural sustainability. This study synthesized a Si-Ca-K-Mg fertilizer (PGF) from PG and evaluated its remediation effects in acidic Cd-polluted soil.</p> Methods <p>The PGF was prepared by thermochemical conversion at 850 °C using PG, biomass ash, potassium sulfate, dolomite, and biochar. Its effects were assessed by soil incubation and lettuce (<i>Lactuca sativa</i>) pot experiments, with measurements of soil properties, Cd speciation, plant physiology, and Cd subcellular distribution.</p> Results <p>The PGF contained Ca₂SiO₄ and CaO, which neutralized soil acidity, eliminated exchangeable Al³⁺, and supplied Si, Ca, Mg, and K. PGF promoted the transformation of exchangeable Cd into Fe–Mn oxide-bound and residual fractions through precipitation and adsorption. In lettuce, PGF alleviated Cd-induced growth inhibition mainly by reducing external Cd stress through soil Cd immobilization and by improving photosynthesis and antioxidant enzyme activities. For residual Cd entering the plant, internal detoxification was associated with redistribution from organelles to cell walls and soluble fractions, where Cd occurred more in pectin- and protein-bound and insoluble forms. Correlation analysis indicated that soil acidity neutralization was closely associated with plant functional recovery, whereas Cd immobilization and nutrient release were associated with lower shoot Cd accumulation and residual Cd compartmentation.</p> Conclusion <p>The PGF prepared by 850 °C carbothermic reduction reduced Cd stress through soil Cd immobilization and supported subcellular compartmentation of residual Cd in lettuce, providing a potential strategy for PG utilization and safe farming in Cd-polluted acidic soils.</p> Graphical Abstract <p></p>