Coenzyme Q10 is an essential cofactor in the electron transport chain and serves as an important antioxidant in both mitochondria and lipid membranes. CoQ10 is also an obligatory cofactor for the function of uncoupling proteins. Furthermore, dietary supplementation affecting CoQ10 levels has been shown in a number of organisms to cause multiple phenotypic effects. However, the molecular mechanisms to explain pleiotrophic effects of CoQ10 are not clear yet and it is likely that CoQ10 targets the expression of multiple genes. We therefore utilized gene expression profiling based on human oligonucleotide sequences to examine the expression in the human intestinal cell line CaCo-2 in relation to CoQ10 treatment. CoQ10 caused an increased expression of 694 genes at threshold-factor of 2.0 or more. Only one gene was down-regulated 1.5-2-fold. Real-time RT-PCR confirmed the differential expression for seven selected target genes. The identified genes encode proteins involved in cell signalling (n = 79), intermediary metabolism (n = 58), transport (n = 47), transcription control (n = 32), disease mutation (n = 24), phosphorylation (n = 19), embryonal development (n = 13) and binding (n = 9). In conclusion, these findings indicate a prominent role of CoQ10 as a potent gene regulator. The presently identified comprehensive list of genes regulated by CoQ10 may be used for further studies to identify the molecular mechanism of CoQ10 on gene expression.