A high specific speed centrifugal pump is used in the situation of large flow and low head. Centrifugal pump parameters need to be optimized in order to raise its head and efficiency under off-design conditions. In this study, the orthogonal experiment design method is adopted to optimize the performance of centrifugal pump basing on three parameters, namely, blade outlet width b2, blade outlet angle β2 and blade wrap angle φ. First, the three-dimensional model of the centrifugal pump is established by CFturbo and SolidWorks. Then nine different schemes are designed by using orthogonal table, and numerical simulation is carried out in CFX15.0. The final optimized combination of parameters is b2 = 24 mm, β2 = 24°, φ = 112°. Under the design condition, the head and efficiency of the optimized centrifugal pump are appropriately improved, the increments of which are 0.74 m and 0.48%, respectively. However, the efficiency considerably increases at high flow rates, with an increase of 6.9% at 1.5 Qd. The anti-cavitation performance of the optimized centrifugal pump is also better than the original pump. The results in this paper can provide references for parameter selection (b2, β2, φ) in the centrifugal pump design.