In this study, the numerical simulation and orthogonal test are combined to study the effects of blade outlet angle, blade inlet angle, and blade number on the centrifugal fan flow characteristics, stress distribution, and noise control. The experimental tests were carried out to confirm the accuracy of the computational model. The computational fluid dynamics (CFD) technology was used to establish 16 groups of impeller models and derive the optimal parameter combination form. The results show that the blade inlet angle and outlet angle have more significant effects on efficiency and flow rate of fans. Among different optimize structures, the A8 fan with an inlet angle of 60°, an outlet angle of 180°, and a blade number of 45, has the best aerodynamic performance, with a 17.4% increase in flow rate, a 3.3% increase in efficiency, a 7.6% reduction in noise and a 23.0% reduction in impeller stress, compared to the original fan. Reasonable adjustment of the inlet and outlet angles greatly improves fluid distribution and suppresses flow separation. Furthermore, the noise can be reduced by lessening the disturbance between the volute tongue and wake flow, so the flow state gets greatly improved at the volute tongue region.