Pressure fluctuation due to rotor-stator interaction in turbomachinery is unavoidable, inducing strong vibration in the equipment and shortening its lifecycle. The investigation of optimization methods for an industrial centrifugal pump was carried out to reduce the intensity of pressure fluctuation to extend the lifecycle of these devices. Considering the time-consuming transient simulation of unsteady pressure, a novel optimization strategy was proposed by discretizing design variables and genetic algorithm. Four highly related design parameters were chosen, and 40 transient sample cases were generated and simulated using an automatic program. 70% of them were used for training the surrogate model, and the others were for verifying the accuracy of the surrogate model. Furthermore, a modified discrete genetic algorithm (MDGA) was proposed to reduce the optimization cost owing to transient numerical simulation. For the benchmark test, the proposed MDGA showed a great advantage over the original genetic algorithm regarding searching speed and effectively dealt with the discrete variables by dramatically increasing the convergence rate. After optimization, the performance and stability of the inline pump were improved. The efficiency increased by more than 2.2%, and the pressure fluctuation intensity decreased by more than 20% under design condition. This research proposed an optimization method for reducing discrete transient characteristics in centrifugal pumps.