Colorectal cancer (CRC) is the third most common malignancy worldwide, and the second leading cause of cancer-associated mortality. The incidence and mortality rates of CRC remain high, posing a significant threat to humans and overall quality of life. Current therapeutic strategies, such as surgery and chemotherapy, are limited due to disease recurrence, chemotherapeutic drug resistance and toxicity. Thus, research is focused on the development of novel treatment approaches. In 2012, ferroptosis was identified as a form of regulated cell death that is iron-dependent and driven by lipid peroxidation. Notably, therapies targeting ferroptosis exhibit potential in the treatment of disease; however, their role in CRC treatment remains controversial. The present study aimed to systematically review the mechanisms and signaling pathways of ferroptosis in CRC, and the specific role within the tumor microenvironment. Moreover, the present study aimed to review the role of ferroptosis in drug resistance, offering novel perspectives for the diagnosis and treatment of CRC.