While the overwhelming number of papers on multi-principal-element alloys (MPEAs) focus on the mechanical and microstructural properties, there has been growing interest in these alloys as solid-state hydrogen stores. We report here the synthesis optimization, the physicochemical and the hydrogen sorption properties of Ti0.325V0.275Zr0.125Nb0.275. This alloy was prepared by two methods, high temperature arc melting and ball milling under Ar, and crystallizes into a single-phase bcc structure. This MPEA shows a single transition from the initial bcc phase to a final bct dihydride and a maximum uptake of 1.7 H/M (2.5 wt%). Interestingly, the bct dihydride phase can be directly obtained by reactive ball milling under hydrogen pressure. The hydrogen desorption properties of the hydrides obtained by hydrogenation of the alloy prepared by arc melting or ball milling and by reactive ball milling have been compared. The best hydrogen sorption properties are shown by the material prepared by reactive ball milling. Despite a fading of the capacity for the first cycles, the reversible capacity of the latter material stabilizes around 2 wt%. To complement the experimental approach, a theoretical investigation combining a random distribution technique and first principle calculation was done to estimate the stability of the hydride.