A previous study highlighted WDR5 as a crucial regulator of histone H3K4 methylation in eukaryotic cells.[30] Expanding on our earlier findings regarding the formation of NSUN5‐WDR5 heterodimers and their collaborative regulation of SMAD3 expression in HCC cells, we investigated whether elevated NSUN5 expression in HCC affects H3K4 methylation via its interaction with WDR5, thereby exerting a corresponding promotional effect. Here, SMAD3 is linked to hepatocellular carcinoma.