Abstract: Objective: To analyze the expression and clinical significance of prohibitin (PHB) in invasive breast cancer (BC) based on high throughput multi-omics databases. Methods: The breast cancer data were downloaded from TCGA and METABRIC databases, and the expressions of PHB in BC tissues and adjacent normal tissues were compared by various bioinformatics tools. The correlations of PHB expression with clinicopathological features and prognosis of BC patients were analyzed, and the interaction and function of PHB protein were predicted. Results: Compared with adjacent normal tissues, PHB was highly expressed in many kinds of cancer tissues, especially in invasive breast cancer where the gene mutation and expression changes of PHB had higher proportion. The expression level of PHB had good diagnostic efficacy for BC (P＜0.01). The expression level of PHB was significantly correlated with the expressions of ER and HER2, PAM50 typing and tumor purity of BC patients (P＜0.05). The survival analysis showed that the high expression of PHB was an independent risk factor of BC (P＜0.01). [STBX]HRAS, KSR1[STBZ] and ARAF interacted with PHB, with significant correlation. The changed expressions of [STBX]HRAS, KSR1[STBZ] and ARAF could be found in BC tissues. Conclusion: The expression of PHB increases in various cancer tissues such as breast cancer, ovarian cancer and so on. The high expression of PHB has significant influence on the prognosis of BC patients. The expression of PHB has good diagnostic efficacy for BC, which may be used as a potential marker for the diagnosis and prognosis of BC.