Breast cancer (BrCa) is a heterogeneous disease, which leads to unsatisfactory prognosis in females worldwide. Previous studies have proved that tumor immune microenvironment (TIME) plays crucial roles in oncogenesis, progression, and therapeutic resistance in Breast cancer. However, biomarkers related to TIME features have not been fully discovered. Proteasome activator complex subunit 2 (PSME2) is a member of proteasome activator subunit gene family, which is critical to protein degradation mediated by the proteasome. In the current research, we comprehensively analyzed the expression and immuno-correlations of Proteasome activator complex subunit 2 in Breast cancer. Proteasome activator complex subunit 2 was significantly upregulated in tumor tissues but associated with well prognosis. In addition, Proteasome activator complex subunit 2 was overexpressed in HER2-positive Breast cancer but not related to other clinicopathological features. Interestingly, Proteasome activator complex subunit 2 was positively related to immune-related processes and identified immuno-hot TIME in Breast cancer. Specifically, Proteasome activator complex subunit 2 was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), immune checkpoints, and tumor mutation burden (TMB) levels. Moreover, the positive correlation between Proteasome activator complex subunit 2 and PD-L1 expression was confirmed in a tissue microarray (TMA) cohort. Furthermore, in an immunotherapy cohort of Breast cancer, patients with pathological complete response (pCR) expressed higher Proteasome activator complex subunit 2 compared with those with non-pathological complete response. In conclusion, Proteasome activator complex subunit 2 is upregulated in tumor tissues and correlated with the immuno-hot tumor immune microenvironment, which can be a novel biomarker for the recognition of tumor immune microenvironment features and immunotherapeutic response in Breast cancer.