The skeleton layout design of assembly jig needs to consider the constraint relationship with assembly products and locators or clamps. Therefore, the design process is complicated and difficult to achieve optimal design. In order to improve the design efficiency and design quality of the skeleton, an optimal layout design method for aircraft assembly jig skeleton based on least square is proposed in this paper. Firstly, the optimal mathematical model of skeleton optimization layout is established based on least square method; then the optimal solution algorithm of the model is established under the different positioning feature distribution situation of assembly products; finally, the optimal layout algorithm of the skeleton is realized based on CATIA system and CAA technology, the effectiveness of this algorithm is verified by the aircraft wing and front fuselage products. The algorithm makes the skeleton layout design simpler and faster, and also be the optimal design result, which can effectively shorten the design cycle and greatly improve the design quality.