The reliability of an electronic package can be described by a physics-of-failure approach. Crack initiation and propagation in the bulk material and interface leads to catastrophic mechanical and finally to electrical failure. Therefore, bulk and interfacial fracture mechanics is a suitable method to describe the reliability of an electronic package. As package, a stud bump bonding flip chip interconnection on a thermoplastic substrate material [liquid crystal polymer (LCP)] is studied. The paper focuses on the description of the interfacial cracking between the underfill and the LCP. This is used to obtain design rules for flip chip interconnection on LCP by means of finite element analysis. Geometry design parameters—fillet shape, chip and substrate sizes—are studied. Moreover, the influence of material properties of the substrate and underfill are investigated. The impacts of the parameters are evaluated by analyzing the energy release rate (ERR) and mode-mixity in the interface. For determination of the critical ERR as function of the mode-mixity, a modified button shear test is utilized. The button, made out of underfill, is cured on the LCP substrate. A pre-delamination is established using a Teflon strip. The critical ERR for different mode-mixities is obtained by varying the shearing height of the button test. Additional, the influence of oxygen plasma treatment of the LCP substrate on the interfacial cracking is taken into account. In the investigation, design rules for increasing the reliability of flip chip interconnections are obtained. Moreover, a modified button-test is applied to obtain critical energy releases rates for different mode-mixities for the interface underfill/LCP. These results are used to optimize the geometry and materials of flip chip interconnections for automotive sensor applications in respect to delamination risk between substrate and underfill.