The ongoing development of hydrogen permeation alloys promotes the wide application of hydrogen energy, especially in the industry of hydrogen production from the water-gas shift reaction (WGS). However, before being widely used, it is still necessary to improve their comprehensive properties, such as hydrogen permeation flux and durability. Pd and its alloy membranes have been deeply studied and have appeared in the market in recent years. Vanadium-based alloys, as a new substitute for these palladium membranes, not only have lower cost but also higher hydrogen permeability. However, huge challenges remain-especially the poor mechanical stability and high susceptibility to hydrogen embrittlement (HE) which is closely related to high absorbed hydrogen concentration of Vanadium. To solve these problems, this paper investigated the structure, hydrogen diffusion, hydrogen dissolution, and hydrogen embrittlement properties of vanadium-based quaternary (V-Nb-Ti-Co) alloys. On this basis, the boundary of ductile brittle transition hydrogen concentration (DBTC) was described. It was found that new phases (such as Co2(V, Nb)3, Co7Nb6 etc.) will be formed in the structure when V is gradually replaced by Nb. Accordingly, the above changes the gradual substitution of V by Nb increased the hydrogen diffusivity and decreased hydrogen absorption. The overall effect is that the permeability decreases first and then increases, but larger hydrogen absorption will weaken the mechanical strength. As a result, the DBTC of the V-Nb-Ti-Co alloys shifts to the right somewhat (about 0.36 (H/M)), expanding the gap of the V-based single-phase alloys. This work demonstrated that the lower limit of DBTC can be adjusted by adding an appropriate amount of Nb in V-based alloys, thus simultaneously increasing the hydrogen permeability and hydrogen embrittlement resistance. This provides help and guidance for the design of novel hydrogen purification alloys.