A methodology that optimizes the hull configuration of a production semi-submersible system is developed in this study, which minimizes the hydrodynamic response of the hull under extreme environmental conditions. The optimization methodology requires the calculation of the hydrodynamic response of different hull prototypes, and then find the optimal hull configuration using the Genetic Algorithm (GA) method. The hydrodynamic response is obtained using the software SESAM, while the GA method is applied using the genetic algorithm toolbox implemented in the software MATLAB. The optimization process is applied to semi-submersible systems for three different oil productions located in Mexican waters of the Gulf of Mexico and designed for the local environmental contour. Six design variables of the semi-submersible hull system are evaluated within the optimization, including the pontoon width and height, the column width and height, the distance between columns, and the draft. This case study confirms that all the evaluated geometric design variables have a high impact on the most probable maximum response (MPMR) and the weight of the hull.