Alternating stress occurs at the crane pedestal structure when FPSO main crane works. The optimization of general layout, yield strength, stiffness and fatigue life should be done in structural design of crane pedestal. Taking main crane pedestal of a deep water FPSO offshore West Africa as an example, the technical requirements of Oil Company’s General Specifications for crane pedestal are introduced. As the requirements of BV Classification Society rules, PATRAN/NASTRAN software is applied to analyze the static yield strength and stiffness of crane pedestal, so that local reinforcement design and Offshore Area of FPSO main crane pedestal and hull interface structure are determined. As the requirements of API, DNV Classification Society rules and Hot Spot Stress method, the fatigue life of typical hot spots of crane pedestal is evaluated by DNV SESAM software. The results show that low cycle fatigue damage caused by crane lifting load is the main part of fatigue damage of typical hot spots on crane pedestal. By improving general layout of FPSO main crane pedestal and local interface structure design, the yield strength, stiffness and fatigue performance of crane pedestal is ensured.