We conclude that, 200 μM hesperetin is likely to stimulate LDLr gene expression via increase phosphorylation of PI3K and ERK1/2, which enhance mRNA levels of the transcription factors, SREBP-1a and SREBP-2, and increased their protein maturation in human hepatoma HepG2 cells. Here, MAPK3 is linked to hepatocellular carcinoma.