Here, our present results from this study provide several lines of evidence supporting the putative role of TEAD4 as an oncogenic protein involved in breast cancer: (a) TEAD4 overexpression promoting DNA synthesis and tumorigenesis in HCC1937 cells; (b) TEAD4 depletion in HCC1806 and HCC1937 suppressing DNA synthesis, cell migration, and tumorigenesis; (c) TEAD4 suppresses the CDK inhibitor p27 gene transcription together with KLF5, an oncogenic transcription factor; and (d) Depletion of p27 significantly rescued the TEAD4 and KLF5 knockdown-induced growth arrest. This evidence concerns the gene KLF5 and breast cancer.