As a special engineering vessel, semi-submersible has high wave resistance and play a very important role in practical marine engineering, which can be applied to various operating conditions. This paper takes the unilateral salvage of wreck by semi-submersible as the background, based on the three-dimensional potential flow theory, and uses the hydrodynamic analysis software Moses to simulate the unilateral lifting and salvage of wreck by semi-submersible. For the salvage operation of a 2240-ton wreck in a 500 m deep water, the motion response of semi-submersible and wreck under different sea conditions is analyzed. Based on the calculation results, the maritime operation conditions of the unilateral salvage method for semi-submersible in this sea area are given, and the calculation results of the suspension force are analyzed, providing useful reference for the arrangement of salvage forces. The relevant research results have high reference value for the selection of operating sea conditions and the allocation of lifting cable forces in the design of unilateral salvage methods for semi-submersible.