Objective To investigate the expression patterns of the perilipin (PLIN) gene family in breast cancer and their associations with immune infiltration and prognosis, thereby identifying potential diagnostic, prognostic, and immunotherapeutic targets for breast cancer. Methods RNA-sequencing data and corresponding clinical information for breast cancer patients were obtained from The Cancer Genome Atlas and the Genotype-Tissue Expression databases. Differential expression of PLIN1-PLIN5 was analyzed using the Wilcoxon test. Receiver operator characteristic curves were generated to evaluate diagnostic performance, and protein expression levels were validated using the Human Protein Atlas database. Associations between gene expression and clinicopathological characteristics were assessed using UALCAN and Bc-GenExMiner v4.5. Prognostic value was evaluated using the Kaplan-Meier Plotter database. The CIBERSORT algorithm was applied to quantify the relative abundance of 22 immune cell types. Pearson correlation analysis was performed to explore the relationship between PLIN1-PLIN5 expression and immune infiltration, followed by functional enrichment analysis. Results Compared with normal breast tissues, PLIN1, PLIN2, PLIN4, and PLIN5 were significantly downregulated in breast cancer tissues, whereas PLIN3 was upregulated. Low expression of PLIN1, PLIN4, and PLIN5 was significantly associated with shorter overall survival and relapse-free survival. Immune infiltration analysis revealed that members of the PLIN family were significantly correlated with multiple immune cell subsets within the tumor immune microenvironment. Specifically, PLIN1 and PLIN5 expression showed positive correlations with activated CD4+ T cells, M1 macrophages, and activated myeloid dendritic cells. PLIN3 expression was positively correlated with M1 macrophages, activated natural killer cells, and CD8+ T cells, but negatively correlated with M2 macrophages. Functional enrichment analysis indicated that PLIN-related genes were enriched in epithelial-mesenchymal transition, inflammatory response, and transforming growth factor-β signaling pathways, suggesting that the PLIN family may participate in immune evasion processes in breast cancer by regulating immune cell recruitment. Conclusions Comprehensive bioinformatics analysis indicates that PLIN1, PLIN4, and PLIN5 may serve as promising prognostic biomarkers for breast cancer and are closely linked to immune infiltration in breast cancer, suggesting their potential as therapeutic targets.