A method for determining the pressure pulsation amplitude of a draft tube of a prototype mixed-flow water turbine is used for predicting the operating stability of a mixed-flow hydraulic power plant under all operating conditions. The stability of the prototype water turbine can be accurately predicted at the research and development stage of the prototype water turbine. The method is implemented based on the relative flow rate and the relative pressure pulsation amplitude of a runner blade outlet velocity head; a curve reflecting the pressure pulsation nature of the draft tube of the power station is obtained according to the statistical law; pulsation amplitude of the draft tube is predicted according to operating parameters of the prototype water turbine, and then the stability of an operating zone of a unit is judged. The method for predicting pressure pulsation of the draft tube of the mixed-flow water turbine is established for the first time around the world and has great significance on both operating of the prototype water turbine and research and development of a newly-built power station.