Wounding caused by various stresses is the initial event of plant regeneration. However, the mechanisms underlying the early wounding responses to promote plant regeneration remain largely unknown. Here, we report that the receptor kinase FERONIA (FER) interacts with Topless/Topless-related proteins (TPL/TPRs) to regulate the expression of regeneration-related genes to modulate root tip regeneration. One ligand of FER, rapid alkalinization factor 33 (RALF33), is stimulated by wounding and functions together with FER to promote regeneration. Single-cell sequencing data showed that the low-differentiation cell types in the stele may account for the enhanced regeneration ability in the fer mutant, especially in the columella and quiescent center (QC). Further interaction assays and analysis of the gene expression patterns in low-differentiation cell types confirmed that FER interacts with TPL/TPRs to regulate the expression of downstream regeneration-related genes. One of their downstream targets, an essential transcription factor (TF) in root regeneration, ERF115, acts downstream of FER-TPL/TPRs to control regeneration. Our results suggested a signaling pathway between the early wounding response and regeneration processes in roots.One-sentence summaryRALF33-FER serves as an early signaling module between wounding and regeneration by functioning with TPL/TPRs in roots.