Hydrogen-deformation interactions and their role in plasticity are well accepted as key features in understanding hydrogen embrittlement. In order to understand the nature of the hydrogen-induced softening process in f.c.c. metals, a substantial effort was made in this study to determine the effect of hydrogen on the tensile stress-strain behavior of nickel single crystal oriented for multiple-slips. It was clearly established that the hydrogen softening process was the result of a shielding of the elastic interactions at different scales. Hydrogen-induced softening was then formalized by a screening factor S of 0.8 ± 0.05 for 7 wppm of hydrogen, which can be incorporated into standard dislocation theory processes. The amplitude of softening suggests that the shielding process is mainly responsible for the stress softening through the formation of vacancy clusters, rather than a direct impact of hydrogen. This effect is expected to be of major importance when revisiting the impact of hydrogen on the processes causing damage to the structural alloys used in engineering.