Abstract: Objective To investigate the role of YingYang1 (YY1) in breast cancer progression, particularly during metastasis, and explore the regulatory mechanism of YY1 on the downstream dual-specificity phosphatase 6 (DUSP6)/extracellular signal-regulated kinase (ERK) axis. Methods Bioinformatics analysis was performed to determine the expression of YY1 in breast cancer and related prognosis. The biological function of YY1 was assessed in lentivirus-mediated overexpression and shRNA cell lines through wound healing assay and invasion assay. Lung metastasis was observed in nude mice subcutaneously injected the seleted cells using bioluminescence imaging. The levels of ERK signaling pathway-related genes and epithelial-mesenchymal transition (EMT) markers were measured by Western blot. Furthermore, a dual-luciferase reporter assay was conducted to evaluate the interaction between YY1 and the DUSP6 promoter. Results YY1 expression was significantly high in breast cancer tissues, and elevated levels of YY1 were associated with advanced N and M stages, indicating poor cancer prognosis. YY1 promoted invasion, migration, and EMT in both in vitro and in vivo models of breast cancer. Conclusions As an oncogene, YY1 activates the ERK pathway by targeting DUSP6, thereby promoting breast cancer metastasis. YY1 may serve as a novel therapeutic target for breast cancer.