Taken a semi-submersible platform in the South China Sea as the research object, a finite element model is established based on the SESAM software, the overall structural strength of the platform is calculated, and the stress concentration areas are selected as the key areas for fatigue calculation. The section characteristic loads are selected, and the motion response and the long-term prediction amplitude at the section loads are calculated. In the GeniE module, the local model is established with the SET grouping to replace the submodel calculation used by the Submod module, and the grid in the key areas is refined. The fatigue damages at the nodes are calculated in the Stofat module, and the fatigue life is calculated according to the S-N curve. The results show that the fatigue damages of nodes in Key Area 1 and Key Area 2 of the platform are greater and their lives are shorter. Therefore, during the service of the semi-submersible platform, it is necessary to conduct the regular overhaul and maintenance of key structural parts to ensure the normal operation of the platform.