A cadmium biosorption process was optimized by varying three independent variables pH (4.5-7.5), initial cadmium ion concentration (10-30 mg L^(-1)), and Yarrowia lipolytica dosage (3-5 g L^(-1)) by using a Doehlert experimental design (DD) involving response surface methodology (RSM). For the maximum biosorption of cadmium ion in an aqueous solution by Y. lipolytica, a total of fifteen experimental runs were set and the experimental data fitted to the empirical second-order polynomial model of a suitable degree. The analysis of variance of the quadratic model demonstrates that the model was highly significant. Three-dimensional plots demonstrate relationships between the cadmium ion uptake with the paired variables (when other variable was kept at its optimal level), describing the behavior of biosorption system in a batch process. The model showed that cadmium uptake in aqueous solution was affected by all the three variables studied. The optimum values of the variables were found to be 6.43, 17.56 mg L^(-1) and 3.63 g L^(-1) for pH, initial cadmium ion concentration and biomass dosage, respectively, at a contact time of 40 min. At these optimal conditions, the maximum percentage biosorption of cadmium was predicted to be 48.89. The experimental values were in good agreement with predicted values and the correlation coefficient was found to be 0.9985. It showed that both monolayer adsorption and intra-particle diffusion mechanisms were effective in the cadmium biosorption process. Therefore, it is apparent that the DD involving RSM not only gives valuable information on interactions between the variables but also leads to identification of feasible optimum values of the studied variables.