The phosphogypsum (PG) is a byproduct of the phosphate fertilizers manufacture. The world production estimated to 200 million tons per year induces environmental threats and storage problems, which requires strict policies to limit pollution and encourage its valorization. This paper presents a purification process of the crude PG including treatment with a diluted sulfuric acid, floatation, filtration and washing. The purified PG is used to produce plaster. The process optimization was conducted using a full factorial design. The significant factors considered in the experimental study are temperature (X1), volume of sulfuric acid solution (X2) and PG quantity (X3). The main effects and interaction effects of these factors on the responses of the % P2O5, % F, Total Organic Carbon (TOC) (mg.kg-1) and pH were analyzed. The optimum conditions for X1, X2 and X3 were found to be 60°C, 3 L and 1 kg, respectively and the optimized pH values was found to be 6.2. Under these conditions, 60% of P2O5, 95% of Fluorine and 98% of TOC were removed from PG. The predicted values were found approximately the same as the experimental ones. The plaster produced with purified PG was found to have similar properties to that produced from natural gypsum.