The influences of adding fourteen different solute elements on the tensile mechanical properties of nickel-based single crystals were studied by molecular dynamics simulation, and the influence of solute elements on the plastic deformation mechanism of nickel-based single crystals was revealed. Then, the charge and chemical bond characteristics of solute and matrix atoms were elucidated by first-principles calculation. The results show that the addition of solute elements has both a solid solution strengthening effect and a high temperature softening effect on the nickel-based single crystals. And the addition of solute element Pt improves the high temperature tensile yield strength of nickel-based single crystal, which pins the dislocations and hinders their motion, leading to dislocation entanglement in the nickel-based single crystal and inhibiting the high-temperature recovery of dislocations. The dislocation density in Pt-containing nickel-based single crystals increases, and the increase in the bonding strength of Pt-Ni atomic bonds makes the Pt-containing nickel-based single crystals have higher tensile yield strength. Thus, this study provides a reliable scientific foundation for improving the mechanical properties of nickel-based single crystals.