Exploring Ru-based materials with strong metal-support interaction (SMSI) is a promising method to develop superb activity and long-term durability electrocatalysts for hydrogen evolution reaction (HER). Herein, a heterojunction substrates strategy is proposed to stimulate the intrinsic activity of Ru nanoparticles loading on FeTeO (Ru/FeTeO) by activating the strong metal-heterojunction substrate interaction (SMHSI). Density functional theory (DFT) and in-situ tests uncover that FeTeO heterojunction substrates can further boost the HER activity by modulating the electronic structure and H adsorption energy. Consequently, the as-prepared Ru/FeTeO possesses outstanding HER activity with low overpotentials of 244 and 311 mV to drive 1.0 and 3.0 A cm−2 current densities in 1.0 M KOH seawater solution, respectively, and displays a long-term stability more than 150 h. This work supplies an effective way to stimulate the intrinsic activity of precious metals.