During infection, Salmonella Typhimurium is able to hijack signaling pathways, controlling the cellular growth and proliferation. However, the precise mechanism by which Salmonella Typhimurium infection impacts stem cells and progenitors, responsible for the ability of the intestinal epithelium to renew and repair itself remains unclear. In our study, we used in vivo systemic mouse model and in vitro intestinal organoid model to characterize the changes in the epithelium growth after Salmonella Typhimurium infection. Our data present evidence that compared to other segments (ileum and colon), the cecal crypt is preferentially targeted by the bacteria. Analysis of mRNA expression profile, protein phosphorylation and immunohistochemistry of infected in situ cecal crypts and in vitro organoids, point out an upregulated proliferation, leading to an increase in size. Moreover, EGFR pathways, crucial to primitive cells proliferation, are taken over by the bacteria. As Salmonella express the outer membrane invasin called Rck, able to interact with EGFR, its potential role in the deregulation of intestinal stem cells and progenitors has been investigated. This new mechanism targeting the proliferation of intestinal primitive cells raises questions about the long-term consequences of repeated Salmonella infections on the crypt integrity and its dysregulation in pathologies such as cancer.