The hydrogen evolution reaction (HER) of molybdenum disulfide (MoS₂) is limited in alkaline and acid solution because the active sites are on the finite edge with extended basal plane remaining inert. Herein, we activated the interfacial S sites by coupling with Ru nanoparticles on the inert basal plane of MoS₂ nanosheets. The density functional theory (DFT) calculation and experimental results show that the interfacial S electronic structure was modulated. And the results of ∆G_H* demonstrate that the adsorption of H on the MoS₂ was also optimized. With the advantage of interfacial S sites activation, the Ru-MoS₂ needs only overpotential of 110 and 98 mV to achieve 10 mA·cm^–2 in both 0.5 M H₂SO₄ and 1 M KOH solution, respectively. This strategy paves a new way for activating the basal plane of other transition metal sulfide electrocatalysts for improving the HER performance.