Abstract We provide a global density-dependent 4He–nucleon (DD-αN) interaction to construct the α–nucleus optical model potential (OMP) across a wide range of incident energies. The global parametrization for the DD-αN interaction is obtained based on the proton–4He OMP, which reproduces the elastic scattering cross-section data very well in the incident energies of 12.04–500 MeV per nucleon. Using the present DD-αN interaction, we derive the α–nucleus potential by a folding procedure with the point-nucleon density obtained by a microscopic mean-field model. The density dependence of the DD-αN interaction is fixed phenomenologically to reproduce the α–nucleus elastic scattering cross-section data obtained from 16O, 40Ca, 58Ni, 90Zr, and 208Pb targets at E/A = 10–342.5 MeV. We also show the total reaction cross sections, which are helpful in fixing one free parameter, the renormalization factor for the imaginary part of the α–nucleus potential. Lastly, we show some examples, which clearly demonstrate the validity and power of the present DD-αN approach.