Overexpression of EPB41L4A-AS2 reduced the motility of HNSCC cells in culture and in vivo, and mechanistically, EPB41L4A-AS2 bound to YBX1 in the nucleus, to reduce the stability of SNAI1 mRNA, decreasing EMT progression, while in the cytoplasm, EPB41L4A-AS2 sponged miR-107, promoting LATS2 expression. Here, SNAI1 is linked to head and neck squamous cell carcinoma.