Aiming to solve the problems of easy clogging and high energy consumption of multi-way fertilization devices for liquid manure, a crushing and impurity removal device for liquid manure was designed by combining the physical characteristics of liquid manure and impurities, and building the corresponding test bench. The proposed device could crush flexible impurities such as straw and filoplume and intercept hard impurities with high density. The main structural parameters of the device were determined according to the survey analysis and the theoretical design. The influences of cutter head shape, cutter edge angle, cutter shaft speed, and cutting clearance on the disqualification rate and energy consumption of straw crushing were obtained by a single-factor experiment. Furthermore, the Box–Behnken central composite design method of the response surface was employed to investigate the effects of the cutter shaft speed, cutting clearance, and cutter edge angle on the disqualification rate and energy consumption of straw crushing. In addition, the working parameters of the device were optimized by employing the response surface method. On this basis, the mathematical relationship model among the disqualification rate, energy consumption, and all influencing factors was established. The results show that the optimal combination of working parameters includes a cutter shaft speed of 312 r/min, a cutting clearance of 1.4 mm, and a cutter edge angle of 45°. From the prediction model, the predicted failure rate was 4.15%, and the predicted energy consumption was 47.53 J. The verification experiment was then performed under the optimal combination of working parameters. The obtained disqualification rate was 4.08% and the energy consumption was 47.56 J, which met the design and work requirements.