Ni and its alloys are susceptible to hydrogen embrittlement. In this thesis, the systematic density functional theory investigations have been performed to explore some of the fundamental aspects of how hydrogen interacts with Ni alloys and to aid the development of Ni alloys with improved resistance against hydrogen induced damage intended for use in hydrogen-containing environments. Grain boundary and lattice cohesion plays a critical role in the hydrogen-enhanced decohesion of hydrogen embrittlement mechanism. Firstly, the effects of a comprehensive set of solutes to Ni bulk lattice and GB cohesion have been investigated by means of density functional theory high-throughput calculations to identify the enhancer elements to Ni lattice and GB in our selected solutes. Furthermore, the synergistic effects of H-solute co-segregation , such as, H-Mo, H-C, and H-S, on the GB cohesion have been investigated in detail. In particularly, in the case of H-S co-segregation, the simulated detrimental effect of H-S co-segregation on GB decohesion as well as the S GB segregation contents after heat treatment have been compared to the results from our experimental partner. It has been suggested in a number of recent theoretical investigations at 0 K that hydrogen atoms can accumulate at defects of Ni in a form of clusters. In the second part of this thesis, a combination of density functional theory calculations and embedded atom method simulations has been employed to investigate the configurations of H clusters at defects in Ni at 0 K as well as finite temperatures. Results show that the stability of H clusters in Ni is limited to temperatures below 300 K and that their appearance at the ambient temperature and therefore an impact on possible hydrogen embrittlement mechanisms is unlikely. In the final part, the thermodynamic and mechanical stability of Ni$_3$X type compounds has been determined by density functional theory calculations of formation enthalpies and elastic properties of their L1$_2$, D0$_{22}$ and D0$_{24}$ phases. In addition, the site occupancy behavior and solubility of some key elements in the L1$_2$-structure Ni$_3$Al, Ni$_3$Ti, and Ni$_3$Nb intermetallic compounds have been investigated in detail. The most stable structure for each Ni$_3$X has been identified, which can be used for the investigation of hydrogen embrittlement on Ni precipitates as well as Ni/precipitate interfaces. This thesis revealed the hydrogen-induced embrittling at the atomic scale by taking use of the atomistic simulations, and gained insights into the hydrogen embrittlement mechanisms in Ni-base alloys. The findings provided the theoretical prediction of hydrogen effect on Ni-base alloys and offered a pathway for the design of hydrogen resistant Ni-base alloys.