In order to improve efficiency of a system with three-dimensional flow characteristics, this paper presents a new method that overcomes three-dimensional effects by using two-dimensional CFD and response surface method. The method was applied to shape optimization of cut-off in a multi-blade fan/scroll system. As the entrance conditions of two-dimensional CFD, the experimental values at the positions out of the inactive zone were used. In order to examine the validity of the two-dimensional CFD the distributions of velocity and pressure obtained by two-dimensional CFD were compared with those of three-dimensional CFD and experimental results. It was found that the distributions of velocity and pressure show qualitatively similarity. The results of two-dimensional CFD were used for constructing the objective function with design variables using response surface method. The optimal angle and radius of cut-off were determined as $72.4^{circ}$ and 0.092 times the outer diameter of impeller, respectively. It is quantified the previous report that the optimal angle and radius of cut-off are approximately $72^{circ}$ and 0.08 times the outer diameter of impeller, respectively.