Nowadays, sulfide ores due to the very low solubility in acids and also the production of toxic and harmful by-products are rarely used to extract metals. In this method, Polyoxometalate (POM) was used as a strong oxidizer of sulfur compounds to dissolve sulfide ores and remove toxic impurities. Also, Taguchi's experimental design based on ProMax simulation software assembled was applied for the leaching study of sulfide ores by Polyoxometalate oxidizer from practical scale (pilot) to industrial scale. The optimum conditions to maximize metals extraction from the sulfide ores were obtained as acid concentration; 80 g/l, reaction temperature; 90 ºC, stirring speed; 300 rpm, retention time; 1.0 h, polyoxometalate value; 0.5g/l, acid type; sulfuric acid (H2SO4), grain size;1.0 mm, and polyoxometalate type; [H2W12O40]10-. Under optimized conditions, the highest extraction efficiency of zinc (Zn), copper (Cu), and load (Pb) metals were determined above 85%, 81%, and 83%, respectively. Also, the maximum removal of toxic impurities was obtained above 99.9%.