The cold box is a crucial component for cryogenic distillation in air separation units. With the increasing focus on energy conservation and emissions reduction, the integral hoisting of the cold box has emerged as a viable alternative to traditional cold box installation due to its highly efficient performance, short cycle time, and superior integration capabilities. Nonetheless, there are concerns surrounding the large size and weight of these boxes, as well as their eccentric structure, which can cause significant challenges during the integral hoisting process and pose safety hazards. To address these issues, this paper proposes a method for optimizing the lifting point of an extra-large cold box through dynamic simulation under actual working conditions. Firstly, a transient structure FEM simulation was carried out using multi-type mesh coupling based on the operating conditions of an extra-large cold box. Secondly, the posture and strength of the box during the hoisting process were analyzed to determine the most dangerous working conditions. Finally, the maximum equivalent stress of the trusses was employed as the fitness function of the particle swarm algorithm to optimize the lifting point position in the whole parameter range. The findings indicated that the most dangerous situation during the hoisting process occurred near the 0° working condition in the flip-up process and that optimizing the lifting point position based on this working condition significantly reduced the stress levels on the trusses.