3D MoS2 hollow spheres were successfully fabricated by hydrothermal process. Commercial bulk MoS2 had quite large grain size and preferential (002) grain orientation, while as-prepared MoS2 hollow spheres had refined grain and random grain orientation. Meanwhile, the hydrogen evolution reaction of the commercial bulk MoS2 and as-prepared MoS2 hollow spheres was systematically investigated in acidic solution. The as-prepared MoS2 hollow spheres catalyst exhibited a lower onset overpotential for hydrogen evolution reaction than bulk MoS2. The superior hydrogen evolution reaction activity could be attributed to the unique 3D MoS2 hollow spheres which provided more active edge sites. In addition, 3D MoS2 hollow spheres also exhibited excellent high chemical stability after 1000 potential cycles.