In summary, beyond demonstrating for the first time that HERG1A potassium channel subunit is the predominant and disease-relevant isoform associated to head and neck tumour progression and metastatic spread, this study provides novel insights into the underlying regulatory mechanisms of HERG1 expression in HNSCC with original evidence supporting the involvement of histone acetylation. Here, KCNA3 is linked to head and neck squamous cell carcinoma.