To better evaluate the clinical prognosis of HNSCC patients through these IRDEGs, we selected nine key prognostic genes, including immunoglobulin superfamily member 5 (IGSF5), NK2 homeobox 3 (NKX2-3), hevein-like protein (HLPF), aldehyde dehydrogenase 2 family member (ALDH2), interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), FXYD domain-containing ion transport regulator 5 (FXYD5), cathepsin L1 (CTSL1), interferon alpha and beta receptor subunit 1 (IFNAR1), and ring finger protein 216 (RNF216), using the LASSO method based on 31 survival-related IRDEGs (Figures 6(a)–6(i)). This evidence concerns the gene CTSL and head and neck squamous cell carcinoma.