This study seeks to uncover how SLC16A1 contributes to HNSCC tumorigenesis.<h4>Methods</h4>To elucidate how SLC16A1 drives HNSCC progression via ferroptosis resistance, we performed RNA sequencing on SLC16A1-knockdown HNSCC cells and controls, followed by functional validation. Here, SLC16A1 is linked to head and neck squamous cell carcinoma.