There are great differences in fatigue cumulative damage and strength degradation of TC4 (Ti-6Al-4V) titanium alloy under different working conditions. In order to fully characterize the influence of load parameters, based on Chaboche damage model and improved multiaxial fatigue damage criterion, a new strength degradation model is proposed to predict the multiaxial high cycle fatigue (HCF) life and evaluate the strength degradation of TC4 titanium alloy. Firstly, the proportional and non-proportional multiaxial fatigue experiments of TC4 titanium alloy under five kinds of loading paths are carried out. The nonlinear multiaxial fatigue damage computation and life prediction of TC4 titanium alloy are conducted via union of the critical plane method and Chaboche damage criterion with the improved damage control parameters. Secondly, a cumulative damage based modified strength degradation model is further established, and it is proved that higher accuracy can be obtained using the model under different load conditions. The experimental results show that, due to considering the influence of load parameters, the accuracy of the prediction results of fatigue life and strength degradation of TC4 titanium alloy proposed in this paper is much higher than other prediction models.