The role of the natural dietary flavonoid chemical quercetin (an antioxidant) in the prevention and treatment of colon cancer is receiving a great deal of attention. However, little is known about the molecular mechanisms of action of this flavonoid. In the present study, whole genome DNA microarrays were used to evaluate the effect of quercetin on gene expression in the CO115 colon‐adenocarcinoma cell line with the completely deleted chromosome 18 harbouring the SMAD4 tumour‐suppressor gene related to colon carcinogenesis. The study demonstrated that quercetin, widely present in fruit and vegetables, inhibited the growth of CO115 cells at 100 μM concentration in both the G1/S and the G2/M phases by modulating cell‐cycle and apoptosis‐related genes. Differential changes in accumulation of transcripts analysed for cells treated with 100 μM quercetin for 24 and 48 h in three independent repeated experiments revealed 5060–7000 differentially expressed genes. This means that quercetin probably does have a broad modulatory effect on gene expression in colon cancer. Out of these differentially expressed genes, the expression of 35 and 23 unique set of genes involved in cell‐cycle control, apoptosis and xenobiotic metabolism were significantly altered after 24 and 48 h quercetin treatment respectively. Our results represent a novel aspect of the biological profile of quercetin that induces cell‐cycle arrest through modulation of cell‐cycle‐related and apoptosis genes. The present study demonstrates a new step in elucidating the underlying molecular mechanisms of the antitumour action of quercetin, which could become a chemopreventive or chemotherapeutic agent for colon cancer.