The deubiquitylase OTUD7B plays a facilitates role in lung tumorigenesis through VEGF protein, but its role in breast cancer remains unclear. In the present study, we proposed to explore the role of deubiquitylase OTUD7B in breast cancer.The expression of OTUD7B in breast cancer and adjacent tissues was detected. The role of OTUD7B in cell proliferation and invasion of breast cancer cell lines such as MCF-7 and MDA-MB-453 was explored.OTUD7B is highly expressed in human breast cancer tissues and its higher expression correlates with better survival of patients. Further mechanistic studies reveal that OTUD7B associates with RASGRF1 and PLCE1 to disrupt RAS signaling pathway. Knockdown of OTUD7B results in decreasing levels of RASGRF1 protein, suppression cell growth and invasion in breast cancer. Collectively, our results reveal a previously unappreciated anti-oncogentic role OTUD7B involved in RAS signaling pathway in breast cancer and indicate that deubiquitylases could induce tumor-suppressing or tumor-promoting activities in a cell- and tissue-dependent context.Copyright © 2024. Published by Elsevier Inc.