We show that the fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides (Asn 105, 157, 258, 330, and 602) via a direct protein‒protein interaction, an action that is necessary for SEMA7A trafficking from the cytoplasm to the cytomembrane and indispensable for HNSCC progression. This evidence concerns the gene SEMA7A and head and neck squamous cell carcinoma.