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We designed a novel nanoparticles-strengthened high-entropy alloy, Ni₃₀Co₃₀Fe₁₃Cr₁₅Al₆Ti₆, which exhibits excellent strength-ductility combinations at both ambient and cryogenic temperatures. Especially at 77 K, an exceptional strength-ductility synergy can be observed, showing an ultrahigh tensile strength of 1.7 GPa and a large ductility of 51%, accompanied by a distinctive three-stage strain-hardening response. The precipitation-hardening behaviors and deformation micro-mechanisms were carefully investigated by the atom probe tomography and transmission electron microscope. The dynamic formation of nano-spaced stacking faults contributed to improved strain-hardening capacities, resulting in simultaneous enhancements of plastic deformation stability and tensile ductility at such high-strength levels.