In silico detection of the TF binding motifs to explore the downstream-regulated molecules of HOX genes and to map it to the driver genes of HNSCC identified 55 possible HOX-target driver genes of HNSCC, which were found to be enriched explicitly in 36 different key signaling pathways such as the MAPK pathway, VEGF pathway, hypoxia response, PI3K pathway, Wnt –signaling pathway, P53 pathway, and apoptosis. Here, TP53 is linked to head and neck squamous cell carcinoma.