Severe trauma or chronic wounds can deplete the keratinocyte stem cells (KSCs) present in the epidermal basal layer or inhibit their migration leading to compromised wound healing. Supplementing KSCs is the key to solution while lineage reprogramming provides a new approach to acquiring KSCs. Through direct lineage reprogramming, induced KSCs (iKSCs) can be produced from somatic cells, which exhibit great application potential. Two strategies are currently being used to directly generate iKSCs, lineage transcription factor (TF)-mediated and pluripotency factors-mediated. This review focuses on lineage TF-mediated direct reprogramming and describes the conversion process along with the underlying epigenetic mechanisms. It also discusses other potential induction strategies to generate iKSCs and challenges associated with in situ reprogramming for skin repair.