Abstract: The prestress loss has a great influence on the integrity and tightness of the containment. As the service age of the containment increases, the prestress loss gradually increases. The operating experience of most nuclear power plants shows that the rate of prestress loss in the containment exceeds even the expected value of the initial design. At present, most scholars evaluate the prestress loss of the containment only at the end of the life of the containment, and there is little research on the safety performance of the containment under different internal pressure after the loss of prestress. From this, the whole life theory to the evaluation method of containment safety performance of nuclear power plants was introduced in this paper. The safety performance of the containment under different levels of internal pressure during the design basis period of 40 years and 60 years following the design basis period was evaluated, taking into account the prestress loss at various ages of the containment. The ABAQUS finite element software was used to create a refined three-dimensional finite element analysis model of the containment, prestress loss calculation based on Concrete Structure Design Code (GB 500102010) and application of prestressing in ABAQUS by the cooling method. The nonlinear finite element method was used to analyze performance indicators such as the yield of the steel liner, the yield of the prestressed tendons, and the evolution of concrete cracks. The findings reveal that when the containment concrete cracks and the steel liner fails, the internal pressure capacity that the containment can withstand is reduced after accounting for prestress loss, and the maximum equivalent plastic strain in the steel liner of the containment is concentrated at the top and bottom sides of the equipment hatch, the crack development of the containment concrete is also more serious than that without considering the prestress loss, and the crack development of the equipment hatch is changed from horizontal to oblique cracks. The deformation of the containment under the ultimate internal pressure is manifested by the outward expansion of the dome and the inward contraction of the equipment hatch. The dome of the containment is severely damaged under ultimate internal pressure. Containment’s deformation increases significantly after considering the prestress loss. However, the containment still has sufficient safety margin under the design internal pressure (0.4 MPa) after 40 years of design base period for containment service and consideration of extending service to 100 years. The above results have implications for the structural design and the assessment of life extension of containment.