The aim of this study was to determine soil properties influence on the heavy metals sorption by vegetables that are used in the diet and possibilities for prediction of their bioaccumulation by response surface methodology (RSM). Lettuce was used as a biosorbent, and cadmium and lead were used as contaminants. Lettuce was grown on compost (previously contaminated with different concentrations of Cd and Pb) which pH was adjusted with different amounts of NPK fertilizers. The content of heavy metals was determined by ICP-MS. Results showed that Cd content in lettuce was below the toxic values, but Pb concentration was above allowable, which indicated that the limit value for Pb is not set in accordance with the food safety regulations. It was found that the heavy metals accumulation in plants depends not only on the content in the soil, but also on the plant affinity for the specific metal, and the individual or the interactive effects of different soil properties. Through the transfer factor it was found that lettuce has a much higher affinity to Cd in relation to Pb. RSM analysis proved to be very good tool for the examination of a large number of variables along with a small number of experiments.