According to the limitation of traditional inverse problem of centrifugal pump blade and its optimization, the free form deformation (FFD) inverse method of centrifugal pump impeller based on load driving was proposed to design the centrifugal pump impeller. A more stable and effective deformation function was established. The centrifugal pump blade load was parameterized by using sectional spline according to the characteristic of centrifugal pump impeller load. The design of experiment was implemented in the designed variables space, and the response surface method was introduced to optimize the distribution of blade load. The three-dimensional transient turbulent flow in pump was simulated by using commercial software. The control and deformation of blade shape and analysis of blade load were implemented by Matlab code. The computation of FFD and CFD was coupled. The relationships between distribution of blade load, blade shape and its hydraulic performance were analyzed. The reasonable distribution of blade load for low specific speed pump blade was deduced. The calculation case results showed that the proposed centrifugal pump blade load optimization theory and method were rational.