We have investigated three-dimensional (3D) MoS2 nanoarchitectures doped with different amount of Ni to boost the hydrogen evolution reaction (HER) in alkaline environment, where this reaction is normally hindered. As a comparison, the activity in acidic media was also investigated to determine and compare the role of the Ni sites in both media. The doping of MoS2, especially at high loadings, can modify its structural and/or electronic properties, which can also affect the HER activity. The structural and electronic properties of the Ni doped 3D-MoS2 nanoarchitecture were studied by X-ray diffraction (XRD), Raman spectroscopy, scanning and transmission electronic microscopy (SEM; TEM), and X-ray photoemission Spectroscopy (XPS). XPS also allowed us to determine the Ni-based species formed as a function of the dopant loading. The HER activity of the materials was investigated by linear sweep voltammetry (LSV) in 0.5 M H2SO4 and 1.0 M KOH. By combining the physicochemical and electrochemical results, we concluded that the Ni sites have a different role in the HER mechanism and kinetics in acidic and in alkaline media. Thus, NiSx species are essential to promote HER in alkaline medium, whereas the Ni-Mo-S ones enhance the HER in acid medium.