In an Iranian zinc smelter plant, nickel and cadmium are removed from the electrolyte solution at the cold purification stage with help of zinc powder. This study tries to investigate the optimal conditions for the removal of these impurities by examining the interactions of effective parameters on the process by the response surface methodology. The results of the experiments showed that cadmium was cemented much more convenient than nickel by the zinc powder. The interplay of parameters showed that increasing the concentration of zinc powder can reduce the time and temperature of the complete reaction. It also neutralized the effect of pH change and mixing speed. The optimum conditions for simultaneous removal of nickel and cadmium were obtained at 75 °C, pH of 4.5, residence time of 45 min, mixing speed of 500 rpm, and 2 g/l zinc powder. Under optimal conditions, more than 99% of nickel and cadmium were removed from the electrolyte solution.