In this study, we show that WHSC1L1 is significantly overexpressed in patients with SCCHN, its knockdown causes cell-cycle arrest and decrease in global H3K36 dimethylation levels, and that it promotes the coordinated transcription of a number of cell cycle genes, including CDK2 and CDC6, which are critical for the G1/S transition. This evidence concerns the gene CDC6 and head and neck squamous cell carcinoma.