Background: Williams Syndrome transcription factor (WSTF) has been implicated in a variety of cellular events. However, the roles of WSTF in human tumorigenesis have not been elucidated. Methods: The molecular and cellular assays were used to identify whether WSTF in MCF-7 cells is a downstream target of Ras-mitogen-activated protein kinase (MAPK) signaling pathway. Results: Ser158 of WSTF was phosphorylated following activation of MAPK signal, suggesting that WSTF may be a downstream target of MAPK signaling pathway. Conclusions: WSTFSer158 (WSTFS158) phosphorylation by Ras-MAPK contributes to tumorigenesis.