The paper presents experimental and numerical characterization of damage evolution for ion-irradiated materials subjected to plastic deformation during nano-indentation. Ion irradiation technique belongs to the methods where creation of radiation-induced defects is controlled with a high accuracy (including both, concentration and depth distribution control), and allows to obtain materials having a wide range of damage level, usually expressed in terms of displacements per atom (dpa) scale. Ion affected layers are usually thin, typically less than 1 micrometer thick. Such a low thickness requires to use nano-indentation technique to measure the mechanical properties of the irradiated layers. The He or Ar ion penetration depth reaches approximately 150 nm, which is sufficient to perform several loading-partial-unloading cycles at increasing forces. Damage evolution is reflected by the force-displacement diagram, that is backed by the stress–strain relation including damage. In this work the following approach is applied: dpa is obtained from physics (irradiation mechanisms), afterwards, the radiation-induced damage is defined in the framework of continuum damage mechanics to solve the problem of further evolution of damage fields under mechanical loads. The nature of radiation-induced damage is close to porosity because of formation of clusters of vacancies. The new mathematical relation between radiation damage (dpa) and porosity parameter is proposed. Deformation process experienced by the ion irradiated materials during the nano-indentation test is then numerically simulated by using extended Gurson–Tvergaard–Needleman (GTN) model, that accounts for the damage effects. The corresponding numerical results are validated by means of the experimental measurements. It turns out, that the GTN model quite successfully reflects closure of voids, and increase of material density during the nano-indentation.