Metformin demonstrated anti‐tumor effects in HNSCC cell lines by inhibiting cell proliferation (> 50% reduction, dose‐dependent), inducing G0/G1 cell cycle arrest, and promoting apoptosis. Mechanistically, these effects were linked to the activation of AMPK and inhibition of the mTOR pathway, supporting its potential as an anti‐cancer agent in preclinical models. This evidence concerns the gene MTOR and head and neck squamous cell carcinoma.