Polymer-metal hybrid (PMH) by over-molding is a kind of weight reduction technology, in which the interface is formed by injecting liquid polymer directly on the surface of stamped metal and then curing under pressure. This technique takes the advantages of both the high strength and stiffness of metal and the complex geometry formability of polymer, and it is usually applied in structural components for weight reduction compared to all-metal structure. However, the different coefficient of thermal expansion (CTE) or hygroscopicity for polymer and metal in PMH structure may possibly produce additional interface stress and decreae joining strength degradation, and finally lead to local separation or complete fracture undervarious environmental loads. The present paper will provide an effective numerical method and investigate the influence of temperature and humidity on the onset and growth of crack, as well as the degradation of interface fracture toughness in PMH structures. Additionally analytical analysis provides qualitative guidelines and orientation for numerical method. The crack initiation is studied by the tensile test of a lap joint specimen, and the crack growth is studied by the DCB (Double Cantilever Beam) test and ENF (End Notched Flexure) test and of PMH specimen with an initial crack. It proves that both temperature and humidity has a great influence on interfacial strength, ultra bearing capacity and energy release rates of PMH structures, and their coupling has more influence than a single factor. The interface degradation degree of the GF30/PA66-HSS is lower than that of PA66-HSS under the same hygrothermal environment.