Recombinant Saccharomyces cerevisiae expressing metallothionein was used for biosorption of lead (Pb). The Plackett-Burman design (PBD) and Box-Behnken design (BBD) were applied to optimize adsorption conditions of Pb by genetically engineered S. cerevisiae. The PBD and its subsequent statistical analysis indicate that the initial concentration of Pb, pH and concentration of biosorbent were the three critical factors influencing Pb biosorption by genetically engineered S. cerevisiae. The Path of steepest ascent was then used to approximate the optimal levels of the main factors. Then, the response surface method was used to optimize the adsorption conditions further. Considering biosorption quantity of Pb as the response objective, a quadratic model was obtained by BBD for 3 factors. The optimal biosorption conditions were as follows: the initial concentration of Pb (81.12 mg/L), pH 5.05 and the concentration of biosorbent (0.15 g/L). Under optimal conditions, the maximum adsorption quantity of Pb is 129.60 mg/g. Model validation experiments showed good correlation between the predicted values and experimental values. The performance of adsorption of Pb by genetically engineered S. cerevisiae is clearly improved by response surface methodology optimization. Genetically engineered S. cerevisiae show higher adsorption capacity than other reported biosorbents and may therefore be an effective biosorbent for industrial use.