Keratin 19 (KRT19), a type I cytoskeletal intermediate filament protein, plays a pivotal role in the structural integrity and cellular functions of epithelial tissues. Beyond its conventional role in cytoskeletal organization, KRT19 has emerged as a significant biomarker and regulator in cancer biology, especially in epithelial malignancies such as oral squamous cell carcinoma (OSCC). Epithelial plasticity, reflecting the dynamic transition between epithelial and mesenchymal states, alongside cancer stemness, is critical for OSCC progression, metastasis, and therapeutic resistance. KRT19 modulates these processes by interacting with key molecular pathways, including the β-catenin/RAC1 complex and NOTCH signaling, thereby influencing cellular proliferation, invasion, and the maintenance of cancer stem cell-like properties. In vitro studies with OSCC cell lines demonstrate that KRT19 affects tumor cell behavior by regulating stemness markers and epithelial-mesenchymal transitions, ultimately impacting tumor aggressiveness and drug resistance. This review consolidates current knowledge on KRT19 biology, its function in epithelial plasticity and cancer stemness within OSCC, and highlights the potential of KRT19 as a prognostic biomarker and therapeutic target. Future research directions include elucidating the precise molecular mechanisms of KRT19-mediated signaling and exploring targeted interventions to mitigate OSCC progression.