The pile is a widely used reinforcement device in geotechnical engineering. For the present paper, we propose a new solution for calculating the safety factor (SF) of the 3D slope reinforced with piles and determining the critical slip surface (CSS) in the framework of minimum potential energy method. In particular, the mobilized shear stress on failure surface is determined by the equilibrium equation of forces operating on slip body. Meanwhile, the moving direction of 3D slope is equivalent to the direction of combined force acting on slip body. Additionally, the present method is combined with the genetic algorithm to identify CSS, and a novel criterion is proposed to locate the shape and position of CSS of a 3D slope using the total potential energy of landslide system as the objective function. The validation and comparison of results indicate that the SF obtained by the introduced method are close to reference solutions, and SF shows an obvious negative correlation with sliding direction (SD). It is also found that the support effect of pile is related to the pile location and the pile density. Meanwhile, the optimal pile position depends on the shape of failure surface and shear strength parameter of soil. Moreover, the effects of some parameters on SD of 3D slopes reinforced with piles are also studied.