This paper proposes a study on the hull structure optimization of a semi-submersible medical platform. The hull structure sizes have great important effect on the cost, hydrodynamics, global, and manufacture of the whole semi-submersible platform. In this paper, the economy, lightweight and higher stability should be ensured for the medical platform during the optimization design process. The hull sizing optimization process is modeled as a multivariable minimization problem, which is minimizing the hull structure weight, the heave response, and the roll response. The surrogate model method is introduced to obtain the relationship between the design variables and output variables, which reduced the time-consuming induced by the numerical simulation and improved the optimization efficiency. A multi-objective optimization for the hull structure is developed by using the gray correlation analysis to evaluate the weight of three optimization objects. At last, the optimization solutions are achieved in the form of Pareto set. According to the optimization results, the changing relations between the sizes of the deck, column, pontoon and draft with the total weight, and the heave and roll response can be determined.