Optimization design of centrifugal pumps involving multiple parameters and objectives is a complicated research topic. The orthogonal method is introduced in the present study to find a high efficiency and low cost way in the optimization process of a centrifugal pump. A orthogonal table designation L₁₆(4⁵) is established, in which 16 individuals of impellers are generated with five design parameters: blade wrap angle, blade angles at impeller inlet and outlet, blade leading edge position, and blade trailing edge lean varying at four levels for each parameter. To realize the multiobjective optimization of both pump efficiency and cavitation performance, an integrated factor considering the weight of two objectives is introduced. On the basis of validated computational fluid dynamics (CFD) technique, the range analysis gives the influence order of five parameters and also determines the value of each parameter. Finally, the optimal centrifugal pump is obtained with remarkable superiority on the efficiency of 3.09% rise and cavitation performance of 1.45 m promotion in comparison with the original pump.