Proteasome activator subunit 3 (REGγ) has a key role in breast cancer by promoting protein proteolysis, but methods to block REGγ expression remain elusive. In this study, we found that the expression of REGγ is significantly upregulated in breast cancer, and that the knockdown of REGγ expression suppresses cell proliferation and induces apoptosis in vitro. Furthermore, REGγ was identified as a direct downstream target of miR-7-5p, and there was an inverse correlation between the expression of REGγ and miR-7-5p. The overexpression of miR-7-5p inhibited cell proliferation and induced apoptosis by mainly targeting REGγ in vitro and in vivo. Our data indicate that miR-7-5p has a critical function through blocking REGγ in breast cancer cells.