This paper firstly establishes a finite element model of a fuselage panel, and then an assembly variation model is derived from the method of influence coefficients (MIC) and principal component analysis (PCA). With the calculation of Fisher information matrix and effective independence (EFI), 49 measurement points are extracted from a number of finite element nodes by the optimum selection method, and the mathematical relation between the position errors of measurement points and the positioning errors of frames is established, which is utilized to analyze the impact of positioning errors of each frame on fuselage panel assembly variation. Finally, the key frame that is important to ensure assembly accuracy and to improve the assembly process is determined.