The computational fluid dynamics (CFD) method has been adopted to optimize the twin-skeg hull line of the twin-skeg Ro-Ro ship from the wake uniformity and the resistance in view of the technical problem that it is difficult to optimize the stern line of the twin-skeg ships. The wake objective function and the average wake fraction proposed by MARIN are used as the evaluation criterion for the wake uniformity. It analyzes the effects of the angle of run of the skeg at 0.8 R above the stern shaft, the fillet radius for the skeg, and the distance between the propeller disk and the stern shaft outlet on the wake uniformity and the resistance. The results show that with the basically constant ship form parameters, the variation of the skeg characteristic parameters will cause the change of the wake uniformity, average wake fraction and resistance. The twin-skeg hull lines are also optimized by the comparative analysis.