Accurately predicting the fatigue life of materials and components is of great significance for ensuring the safety of mechanical equipment. In most strain-controlled fatigue experiments, before fatigue fracture occurs, plastic strain accumulation and microstructure changes have a great impact on the cyclic stress–strain response of the material, which manifests as a hysteretic loop evolution. In this paper, the cyclic hardening/softening tendency under different strain amplitudes, the loss mechanism of the loading modulus and unloading modulus, as well as the evolution law of plastic strain energy of 45CrNiMoVA steel were investigated. A life prediction model based on the modified plastic strain energy was proposed according to the evolution law of plastic strain energy. The results showed that the prediction error of the modified plastic strain energy model was within the 2 times error band, which decreased significantly from 13.73% to 7.68% after parameters correction compared with the prediction error of the strain-based prediction model.