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After acute wound formation, the oxygen supply is reduced, which results in the formation of an acute hypoxic microenvironment; whether this hypoxic microenvironment enhances epidermal cell migration and the underlying regulatory molecular mechanism of this effect are unclear. In this study, HaCaT cells were maintained under hypoxic (1% oxygen) or normoxic conditions. Methods including immunofluorescence staining, wound scratch assays, transwell assays, Western blotting and high‐ and low‐expression lentiviral vector transfection were utilized to observe the changes in cell migration, microtubule dynamics and the expression levels of microtubule‐associated protein (MAP) 4 and the light chain protein DYNLT1 (Tctex‐1). The possible mechanisms were studied and discussed. The results showed that epidermal cell migration was enhanced during early hypoxia. Further experiments revealed that MAP4 regulates microtubule dynamics and promotes epidermal cell migration through Tctex‐1. MAP4 and Tctex‐1 play important roles in regulating the migration of epidermal cells under hypoxia. This evidence will provide a basis for further revealing the cellular and molecular mechanisms of local wound hypoxia and for promoting wound healing. [ABSTRACT FROM AUTHOR]