In the present work, a probabilistic framework for fatigue life prediction and reliability assessment of an engine high pressure turbine disc is proposed to incorporate the effects of load variations and mean stress, which provides a reference for engine structural design under a given target failure probability. Within this framework, a new probabilistic fatigue damage accumulation model under random loadings is elaborated based on a ductility exhaustion model, and probabilistic [Formula: see text] curves for the high pressure turbine disc under different flight missions are derived based on experimental data of turbine disc alloy GH4169. The influence of random load variations on fatigue reliability of the high pressure turbine disc has been investigated and quantified by combining the engine load spectrum with finite element analysis.