PURPOSE: The dysregulation of the cytoplasmic poly(A)-binding protein 1 (PABPC1) is involved in a variety of tumors but little is known about its role in human breast cancer. Therefore, the effect of PABPC1 in the prognosis and regimen selection in breast cancer patients was evaluated. METHODS: A total of 791 cases of invasive breast cancer were included in this study, although only 416 were involved in subsequent analyses after the propensity score matching (PSM) test. PABPC1 expression was detected by immunohistochemistry. The relationship between PABPC1 expression and clinicopathological factors, postoperative regimens, and outcomes was determined. RESULTS: In the total 791 cases, 583 cases were positive for PABPC1, but only 212 (26.8%) showed high PABPC1 expression (PABPC1-HE). The overall survival (OS) and disease-free survival (DFS) of PABPC1-HE patients after PSM were significantly worse than those in patients with PABPC1 low expression (PABPC1-LE), regardless of age, molecular type, tumor size, nodal status, or pStage. Postoperative chemotherapy (CT) increased the OS of PABPC1-HE patients but not that of PABPC1-LE patients. Among patients receiving endocrine therapy, those in the PABPC-LE group had an extended OS, while CT or chemoradiotherapy (CT/CRT) only significantly extended the OS time of PABPC-HE patients. CT/CRT did not significantly extend the survival of PABPC1-LE HER2-positive patients but extended the OS of PABPC1-HE HER2-positive patients. However, the OS of patients treated with CT/CRT + trastuzumab therapy was significantly longer than that of other patients under other therapies in the PABPC1-HE group, suggesting that PABPC1-HE might be sensitive to trastuzumab-based therapy. The multivariate analysis revealed that PABPC1-HE was an independent prognostic factor for both poor OS and DFS in breast cancer except luminal A type. CONCLUSIONS: Our results revealed that PABPC1 might be considered as a biomarker to help in subtyping, as well as in the prognosis and regimen selection of breast cancer patients.