Background Wound re-epithelialization is considered as an extremely important link in the complete reconstruction of the epidermal barrier. The present study is aimed to determine the association between transforming growth factor β (TGF-β) and re-epithelialization. Objective It was aimed to explore the possible molecular mechanism of TGF-β mediated re-epithelialization. Results NEAT1 was upregulated in TGF-β1-treated HaCaT cells and promoted cell proliferation. NEAT1 overexpression enhanced the wound healing and upregulated MMP-2 and MMP-9 in TGF-β1-treated HaCaT cells. Mechanically, TGF-β1 down-regulated miR-26a-5p through targeting NEAT1 in HaCaT cells. Furthermore, NEAT1/miR-26a-5p axis regulated the expression of LGR4 in HaCaT cells. Finally, the results showed that NEAT1/miR-26a-5p/LGR4 axis was involved in TGF-β1-mediated re-epithelialization. Conclusion NEAT1/miR-26a-5p/LGR4 network is an important participant in TGF-β1-mediated keratinocyte proliferation and migration, which provides a novel perspective for understanding the cellular behavior and related molecular events in re-epithelialization.