Colorectal cancer I Endogenous opioid system I Opioid receptors I Opioids I Opium Abbreviations COX-2 cyclooxygenase-2. _ CRC colorectal cancer. _ DCs dendritic cells. _ DEN diethylnitrosamine. _ GPCR Gprotein-coupled receptors. _ IBD inflammatory bowel disease. _ IL-1β interleukin 1β. _ IL-6 interleukin 6. _ MMT methadone maintenance treatment. _ MOR mu opioid receptor. _ n-Cdh n-cadherin. _ NK natural killer cell. _ Nx propofol with epidural anesthesia. _ PGE2 prostaglandin E2. _ TJ tight junction. _ TLR toll-like receptor. _ TNFα tumor necrosis factor α. _ TPA 2-o-tetradecanoyl-phorbol-13-acetate. _ uPA urokinase plasminogen activator. _ ZO zonulaoccludens. Opinion statement So far, opioids have been successfully used to reduce cancer pain in patients in order to improve their quality of life. However, the use of opioids leads to numerous side effects such as constipation, drowsiness, nausea, itching, increased sweating and hormonal changes. In this review, we described the action of opioids in several molecular pathways significant for maintenance of the intestinal homeostasis including the impact on the intestinal epithelium integrity, changes in microbiome composition, modulation of the immune system or induction of apoptosis and inhibition of angiogenesis. We summed up the role of individual opioids in the processes involved in the growth and development of cancer and elucidated if targeting opioid receptors may constitute novel therapeutic option in colon cancer.