Therefore, the aims of the present study were to explore the interactions among AMPK/ACC, AMPK/PERK/eIF2α, and TRPP2/PERK/eIF2α signaling pathways and whether TRPP2 knockdown affects the AMPK signaling pathway and proliferation of HN-4 cells, cell line originating from human oral, and hypopharyngeal squamous cell carcinoma. The gene discussed is EIF2AK3; the disease is hypopharynx squamous cell carcinoma.