Increasing evidence has reported the critical roles of PIEZO1 in organism. However, the knowledge of PIEZO1 in human cancers is still inadequate.In silico analyses and experimental validation were performed to analyze PIEZO1's expression, prognostic values and potential upstream/downstream mechanism in breast cancer.PIEZO1 was significantly overexpressed in human breast cancer cell lines and tissue samples. PIEZO1 expression was statistically positively associated with malignant progression and short survival of breast cancer. miR-10b-5p downregulation was partially responsible for PIEZO1 upregulation in breast cancer. Further exploration revealed that PIEZO1 might exert its function by regulating purine metabolism (especially GUK1, POLD1 and APRT) in breast cancer.Collectively, the current study elucidated an important role of PIEZO1 in breast cancer and providing key clues for identifying PIEZO1 as a therapeutic target and prognostic biomarker in breast cancer.