Hydroelectric generator unit is a complex mechanical system which is composed of hydraulic turbine and electric generator. Rotary system is supported by the bearing bracket and the reinforced concrete structures, and vibration problem can't be avoided in the process of operating. Many large-scale hydroelectric units have been damaged because of the vibration problem in recent years. As the increase of the hydraulic turbine unit capacity and water head, the safe operation of hydraulic turbine has become a focus research in many countries. The operating characteristics of the hydraulic turbine have obvious differences at different working conditions. Based on the combination of field measurement and theoretical calculation, this paper shows a deep research on the safe operation of a large-scale Francis turbine unit. Firstly, the measurements of vibration, swing, pressure fluctuation and noise were carried out at 4 different heads. And also the relationships between vibrations and pressure fluctuations at different heads and working conditions were analysed deeply. Then the scientific prediction of safe operation for the unit at high head were done based on the CFD numerical calculation. Finally, this paper shows the division of the operating zone for the hydroelectric unit. According to the experimental results (vibrations, swings, pressure fluctuations and noise) as well as the theoretical results, the operating zone of the unit has been divided into three sections: prohibited operating zone, transition operating zone and safe operating zone. After this research was applied in the hydropower station, the security and economic efficiency of unit increased greatly, and enormous economic benefits and social benefits have been obtained.