According to our KEGG pathway analysis, miR‐99a‐5p significantly affected the progression of HNSCC by regulating the PI3K‐Akt signaling pathway, of which the predicted target genes, phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit data (PIK3CD), insulin‐like growth factor 1 receptor (IGFR1), platelet‐derived growth factor receptor, beta polypeptide (PDGFRB), and mechanistic target of rapamycin (MTOR) were involved. Here, AKT1 is linked to head and neck squamous cell carcinoma.