Grain boundary engineering plays an important role in the design of new polycrystalline materials with enhanced mechanical properties. For instance, the resistance against hydrogen embrittlement of nickel-base alloys can be improved by aimed grain boundary segregation. A purposeful application of this approach requires a profound knowledge about the segregation tendencies. Therefore, atom probe tomography is applied to reveal the grain boundary chemistry at the atomic level of a nickel-base model alloy, whereby the segregation behaviour of individual elements is evaluated through the interfacial excess value. Precipitation formation must be carefully considered for all elements to exclude influences on the interpretation of segregation. For cross-validation a DFT-based model approach is used to predict the expected segregation tendencies based on the applied heat treatment and chemistry. This overall approach can be used to design new hydrogen embrittlement resistant materials for future usage in hydrogen storage and transportation applications.