Centrifugal blood pumps have provided a powerful artificial support system for patients with vascular diseases. In the design process, geometrical optimization is usually needed to acquire a more biocompatible model for clinical uses. In the current paper, we propose a method for multi-objective optimization concerning both the hydraulic and the hemolytic performances of the pump based on the near-orthogonal array in which the traditional hemolysis index (HI) is replaced with the maximum scalar shear stress criteria to reduce the computation load. The method is demonstrated with the optimization of an extracorporeal centrifugal blood pump with an unshrouded impeller. CFD studies on the original and nine modified pump models are carried out. The calculated hydraulic performances of the optimized model are also compared against the experiments for validation of the numeric method, with an error of 3.6% at the original design point. The resulting blood pump with low maximum scalar shear stress (132.2 Pa) shows a low degree of calculated HI (1.69 × 10⁻³).