In order to evaluate the safety of salvage operation, a numerical model of the coupling dynamic response characteristics of the “Yangtze River Estuary II” salvage system is established based on the three-dimensional potential flow theory and the Skempton formula. The model has been verified by actual measurement and is used in the safety analysis of the whole salvage process. The research results show that special attention needs to be paid to the motion response of the salvage system and the tension changes of the lifting and mooring lines in the two stages of bottom-off and partial water-out in the overall salvage process. With the increase of wave height and spectral peak period, the motion response of the salvage system and the extreme value of cable tension increase. The influence of wave direction on the six-degree-of-freedom movement of the system is more complicated, and the extreme value of the tension of the lifting cable increases significantly under the action of oblique waves. According to the calculation of the safety factor of the cable, when formulating a salvage plan, an appropriate lifting speed should be selected, and at the same time, salvage operations should be avoided in waves of 20°—70°.