Breast cancer remains a major global health burden, necessitating improved prognostic markers and therapeutic strategies. This study investigates the role of class II major histocompatibility complex transactivator (CIITA), a master regulator of major histocompatibility complex class II(MHC-II) gene expression, in breast cancer. Although CIITA is well recognized for its role in antigen presentation in immune cells, its function in tumor immunity and prognosis remains underexplored. Through integrative bioinformatics analyses using The Cancer Genome Atlas (TCGA) and other datasets, we demonstrate that high CIITA expression is associated with favorable clinical outcomes and enhanced immune activation in breast cancer. CIITA levels correlate with increased infiltration of antitumor immune cells, elevated expression of immune checkpoint genes, and enrichment of immune-related pathways. Immunohistochemical staining of breast cancer tissues further confirms CIITA protein expression patterns. Moreover, functional enrichment analyses suggest that CIITA may influence tumor-immune interactions by modulating immune response pathways. A prognostic nomogram incorporating CIITA expression shows robust predictive value for overall survival, offering potential clinical utility. These findings highlight CIITA as a promising prognostic biomarker and immunomodulatory target in breast cancer, shedding light on its role in shaping the tumor immune microenvironment.