Proprotein convertase subtilisin/kexin type 9 (PCSK9) posttranslationally promotes the degradation of the low-density lipoprotein receptor (LDLr) in hepatocytes and increases plasma LDL cholesterol. It is not clear, however, whether PCSK9 plays a role in the small intestine. Here, we characterized the patterns of variations of PCSK9 and LDLr in fully differentiated Caco-2/15 cells as a function of various potential effectors. Cholesterol (100 µM) solubilised in albumin or micelles significantly down-regulated PCSK9 gene (30%, p<0,05) and protein expression (50%, p<0,05), surprisingly in concert with a decrease in LDLr protein levels (45%, p<0,05). 25-hydroxycholesterol (50 µM) treated cells also displayed significant reduction in PCSK9 gene (37 %, p<0,01) and protein (75% p<0,001) expression, while LDLr showed a decrease at the gene (30%, p< 0,05) and protein (57%, p<0.01) levels, respectively. The amounts of PCSK9 mRNA and protein in Caco-2/15 cells were associated to the regulation of HMG-CoA reductase and sterol regulatory element binding protein-2 (SREBP-2) that can transcriptionally activate PCSK9 via sterol-regulatory elements located in its proximal promoter region. On the other hand, depletion of cholesterol content by hydroxypropyl--cyclodextrine up-regulated PCSK9 transcripts (20%, p<0,05) and protein mass (540%, p<0,001), in parallel with SREBP-2 protein levels. The addition of bile acids (BA), taurocholate and deoxycholate, to the apical culture medium lowered PCSK9 gene expression (25%, p<0,01) and raised PCSK9 protein expression (30%, p<0,01) respectively, probably via the modulation of farnesoid X receptor. Furthermore, unconjugated and conjugated BA exhibited different effects on PCSK9 and LDLr. Altogether; these data indicate that intestinal PCSK9 is highly modulated by sterols and emphasize the distinct effects of BA species.