Our work highlights a new role of SHP2 in regulating breast cancer progression by enhancing the production and secretion of the pro-metastatic cytokine IL-8. We also provide mechanistic insights into the effects of SHP2 inhibition and its downstream repercussions. Overall, this work enforces the rational for targeting SHP2 in breast cancer in order to reduce local invasion and block the metastatic potential of neoplastic cells.