In conclusion, for the first time, we showed that ETs induced cell toxicity, ROS production, inflammatory gene expression, altered mitochondrial respiration, and upregulates drug metabolic CYP1-A1, CYP1-A2 CYP2-D6, CYP2-E1, CYP3-A4, CYP3-B4, and VEGFA gene expression in HepaRG and HCC HepG2 and SK-Hep1 cells. Here, CYP2D6 is linked to hepatocellular carcinoma.