• Single-crystal-like nanostructure interfaces were achieved via a simple synthetic method. • The prepared nanostructures showed excellent electrocatalytic performance. • The enhanced performance was related to the unique physicochemical properties. • This work offers a promising process to prepare non-precious catalysts for use in acid. Non-precious-metal oxides provide various physical and chemical controllable properties when their composition and morphology are tuned for electrochemical applications. However, the unstable features due to catalytic degradation caused by the dissolution and agglomeration of the materials in acidic media have prevented the widespread use of these materials in electrocatalysis. Herein, we propose a facile and simple method for the synthesis of S and Ni co-doped single-crystal-like iron oxide nanorods (S,Ni_Fe 2 O 3 NR) grown over a MoS 2 substrate. Interestingly, the S,Ni_Fe 2 O 3 NR catalyst demonstrated a stable current density of nearly -100 mA/cm 2 when operated at a constant potential of -0.31 V ( vs . SHE) without structural and chemical deformation of the material. The commercial Fe 2 O 3 showed agglomerated particles after a stability test. In addition, the newly prepared S,Ni_Fe 2 O 3 NR catalyst exhibited excellent catalytic HER performance with an overpotential of -92 mV ( vs . SHE) to reach -10 mA/cm 2 (a Tafel slope of 54 mV/dec). Our density functional theory (DFT) calculations suggest that a heterogeneously mixed surface with Ni and S atoms on the Fe 2 O 3 surface can improve the HER performance. This work provides information about the design and development of future electrocatalysts with non-precious-metal oxides for use in an acidic environment.