Defect engineering is widely applied in transition metal dichalcogenides (TMDs) to achieve electrical, optical, magnetic, and catalytic regulation. Vacancies, regarded as a type of extremely delicate defect, are acknowledged to be effective and flexible in general catalytic modulation. However, the influence of vacancy states in addition to concentration on catalysis still remains vague. Thus, via high throughput calculations, the optimized sulfur vacancy (S-vacancy) state in terms of both concentration and distribution is initially figured out among a series of MoS2 models for the hydrogen evolution reaction (HER). In order to realize it, a facile and mild H2O2 chemical etching strategy is implemented to introduce homogeneously distributed single S-vacancies onto the MoS2 nanosheet surface. By systematic tuning of the etching duration, etching temperature, and etching solution concentration, comprehensive modulation of the S-vacancy state is achieved. The optimal HER performance reaches a Tafel slope of 48 mV dec-1 and an overpotential of 131 mV at a current density of 10 mA cm-2, indicating the superiority of single S-vacancies over agglomerate S-vacancies. This is ascribed to the more effective surface electronic structure engineering as well as the boosted electrical transport properties. By bridging the gap, to some extent, between precise design from theory and practical modulation in experiments, the proposed strategy extends defect engineering to a more sophisticated level to further unlock the potential of catalytic performance enhancement.