Molybdenum disulfide (MoS2) presents a promising catalyst to replace state-of the-art platinum (Pt) for hydrogen evolution reaction (HER), but it still lacks an effective way due to the catalytically inert basal plane. Herein, we report a rational design of MoS2 nanomesh that possesses evenly distributed holes and defects to make full use of the 2H-MoS2 basal planes by combining ball-milling with ultrasonic methods. The exfoliation of muti-layer MoS2 to fewer layer or enven monolayer is proceed in pure water without using any chemicals or surfactants. The great advantage of the catalyst is the monolayer, holey and defective structure, which maximizing the synergistic activity for both electrocatalytic and photocatalytic HER performances. Impressively, the MoS2 nanomesh renders outstanding electrocatalytic HER activity with an overpotential of 160 mV at a current density of 10 mV cm(-2), and a small Tafel slope of 46 mV decade(-1). The photocatalytic H-2 evolution rate is about 4.84 mmol h(-1) when working with Eosin Y as an organic photosensitizer. Additionally, this catalyst shows excellent cycle stability in the electrochemical and photocatalytic reactions. This present work put a new insight into the large-scale production of chemically active 2H MoS2-based catalysts for HER.