Colorectal cancer (CRC) represents the second leading cause of cancer-related deaths worldwide. The pathogenesis of CRC is a complex multistep process. Among other factors, inflammation and oxidative stress (OS) have been reported to be involved in the initiation and development of CRC. Although OS plays a vital part in the life of all organisms, its long-term effects on the human body may be involved in the development of different chronic diseases, including cancer diseases. Chronic OS can lead to the oxidation of biomolecules (nucleic acids, lipids and proteins) or the activation of inflammatory signaling pathways, resulting in the activation of several transcription factors or the dysregulation of gene and protein expression followed by tumor initiation or cancer cell survival. In addition, it is well known that chronic intestinal diseases such as inflammatory bowel disease (IBD) are associated with an increased risk of cancer, and a link between OS and IBD initiation and progression has been reported. This review focuses on the role of oxidative stress as a causative agent of inflammation in colorectal cancer.