Abstract: Helical milling is a common hole-making technique for CFRP/Titanium alloy laminated structural parts, however, the difference in cutting performances between two materials makes it difficult to guarantee machining quality with a single parameter. In this paper, a variable parameters helical milling technique was proposed to meet the practical demand for precision hole-making of laminated structures. By analyzing the transitional thrust force, the interfacial quality and the interfacial aperture, the influence of hole-making sequence and variable parameters position on the interfacial machining characteristics was investigated deeply. The results indicate that, the hole-making sequence had a significant influence on the transitional thrust force, the interfacial machining quality and the interfacial hole accuracy, while the variable parameter position mainly affected the interfacial quality. The optimal interfacial quality could be achieved by the use of C/Ti-C hole-making scheme, with an interfacial flatness factor of only 8% of the Ti/C-Ti method. And the smallest difference in the interfacial aperture between CFRP and Titanium alloy was achieved, only 29 μm, with the Ti/C hole-making sequence. Based on the comprehensive consideration of interfacial quality and dimensional accuracy, the C/Ti-C variable parameters scheme should be chosen.