Hydrogen energy from solar water-splitting is known as an ideal method with which to address the energy crisis and global environmental pollution. Herein, the first-principles calculations are carried out to study the photocatalytic water-splitting performance of single-layer GaInSesub.3 under biaxial strains from −2% to +2%. Calculations reveal that single-layer GaInSesub.3 under various biaxial strains has electronic bandgaps ranging from 1.11 to 1.28 eV under biaxial strain from −2% to +2%, as well as a completely separated valence band maximum and conduction band minimum. Meanwhile, the appropriate band edges for water-splitting and visible optical absorption up to ~3 × 10sup.5 cmsup.−1 are obtained under biaxial strains from −2% to 0%. More impressively, the solar conversion efficiency of single-layer GaInSesub.3 under biaxial strains from −2% to 0% reaches over 30%. The OER of unstrained single-layer GaInSesub.3 can proceed without co-catalysts. These demonstrate that single-layer GaInSesub.3 is a viable material for solar water-splitting.