A brown seaweed consumed worldwide, Fucus vesiculosus, has been used to prevent atherosclerosis and hypercholesterolemia, among other uses, however, the mechanisms of action that lead to these effects are not yet fully understood. An F. vesiculosus aqueous extract, prepared as a soup was characterized as rich in sev-eral bioactive compounds, mainly phlorotannin and peptides. This work aims to study the in vitro effect of this extract on the expression of different proteins involved in the synthesis and transport of cholesterol in HepG2 cells, though a proteomic analysis, western blot and qRT-PCR. The results demonstrated that, in liver cells, the extract decreases the expression of 4 proteins involved in cholesterol biosynthesis process and also decrease the expression of two important transporters proteins of cholesterol, NPC1L1 and ABCG5, as well as decrease the NPC1L1 mRNA levels. Our study demonstrates some mechanisms of action of bioactive com-pounds from F. vesiculosus that may explain its previously reported hypocholesterolemic effect.