The irradiation damage behaviors of single crystal (SC), coarse-grained (CG), and nanograined (NG) copper (Cu) films were investigated under Helium (He) ion implantation at 450 °C with different ion fluences. In irradiated SC films, plenty of cavities are nucleated, and some of them preferentially formed on growth defects or dislocation lines. In the irradiated CG Cu, cavities formed both in grain interior and along grain boundaries; obvious void-denuded zones can be identified near grain boundaries. In contrast, irradiation-induced cavities in NG Cu were observed mainly gathering along grain boundaries with much less cavities in the grain interiors. The grains in irradiated NG Cu are significantly coarsened. The number density and average radius of cavities in NG Cu was smaller than that in irradiated SC Cu and CG Cu. These experiments indicate that grain boundaries are efficient sinks for irradiation-induced vacancies and highlight the important role of reducing grain size in suppressing radiation-induced void swelling.