Our study identified a novel functional variant rs3094187 associated with SCCHN risk, which could modify TCF19 expression by regulating the binding affinity of the transcription factor SREBF1. Further functional investigations demonstrated that TCF19 was overexpressed in SCCHN and the inhibition of TCF19 might attenuate the proliferation and migration of SCCHN cell lines, as well as the growth of xenograft tumors in a mouse model. These findings support TCF19 may act as a putative SCCHN susceptibility gene. (By Xiaoyu Wei and Professor Hongxia Ma, https://jmg.bmj.com/content/early/2021/03/05/jmedgenet-2020-107410 )