In this research, we identified that DDX17 in hepatocytes is a novel NASH promoter that stimulates lipid accumulation, inflammation and fibrosis in the liver by cooperating with DDX5 and CTCF in order to repress the transcription of Cyp2c29, which ultimately diminishes the production of 14,15‐EETs. Here, DDX5 is linked to metabolic dysfunction-associated steatohepatitis.