This paper makes the energy consumption difference analysis of the key parameters variations of a 1000MW Ultra-Supercritical Double Reheat coal-fired power generation system. By applying the constant power variable condition calculation method for the steam turbine thermal system, the energy consumption difference analysis mode is established. The energy consumption difference of the key parameters variations (such as the main steam pressure, the main steam temperature and the exhaust steam pressure) of a 1000MW ultra-supercritical double reheat coal-fired power generation system at THA load, 75%THA load, 50%THA load and 40%THA load are investigated. The effects of the key parameter changes on the gross turbine heat rate and coal consumption rate at different working conditions are analyzed, as well as the corresponding energy consumption variation characteristic curves, and the variation rules of power generation efficiency are explored. In addition, the energy consumption difference variation rules of system at different working conditions are studied when any two key parameters such as the main steam temperature, main steam pressure, and the exhaust pressure change simultaneously. The research results show that within a certain range of variation, when the main steam temperature or the main steam pressure increase, or the exhaust gas pressure decreases, the energy consumption of the overall system drops. And with the reduction of load, the main steam temperature has the greatest influence on the coal consumption. By studying the effects of the simultaneous change of two key parameters on the energy consumption of the overall system, it is found that under the same load, the change of the exhaust gas pressure has the greatest influence on the system energy consumption. This paper will provide the theoretical guidance for the energy-saving diagnosis and operation optimization of ultra-supercritical double reheat coal-fired power generation system.