Except for its clinical value, we confirm that targeting USP10 (gene depletion and antagonist) inhibits the growth of HNSCC in vitro and in vivo, identification of USP10 as suppressor of ferroptosis could have potential clinical translational implications for cancer target therapy, with the consideration that inhibitors of DUBs have already been approved by the FDA or widely researched in the clinic. Here, USP10 is linked to head and neck squamous cell carcinoma.