Lignin is one of the components in the plant cell wall, after cellulose, making up 20-30% of the global plant biomass. Lignophenols (LPs) are derivatives of lignin with high phenolic function and antioxidant properties. However, their medicinal property is not well characterised. Apolipoprotein-B (apo-B) is an essential component in very low-density lipoprotein, and high levels of serum apolipoprotein-B (apo-B) are a major factor for coronary heart disease. In this study, we examined the effect of lignophenols on apo-B secretion in HepG2 cells. HepG2 cells were treated with varying concentrations of LPs and 0.8 mm sodium oleate. LPs decreased oleate-induced apo-B secretion in a dose-dependent manner. LPs also decreased oleate-induced microsomal triglyceride transfer protein (MTTP) mRNA expression and cellular total cholesterol, suggesting that lipid bioavailability and lipidation of lipoprotein are likely involved in the decreased secretion of apo-B. Furthermore, LPs decreased oleate-induced mature sterol regulatory element binding protein 2 (SREBP-2), a transcription factor that activates cholesterol biosynthesis. This is the first study to show that LPs can decrease oleate-induced apo-B secretion in HepG2 cells. The modulations of MTTP mRNA expression, cellular total cholesterol metabolism and mature SREBP-2 expression may be important factors in the regulation of apo-B secretion by LPs.