OBJECTIVE The review aims at elucidating the role of lipid peroxidation of polyunsaturated fatty acids (PUFAs) in colorectal cancer (CRC) risk and treatment. RESULTS CRC is one of the most overriding threats to public health. Despite a broad range of treatments, up to 50% of patients will inevitably develop incurable metastatic disease. Peroxidation of PUFAs contributes to augmentation of oxidative stress and causes in consequence inflammation, which is one of the possible carcinogenic factors of CRC. End products of PUFAs might be used as biomarkers for CRC detection and surveillance for treatment. They also have cytotoxic effect in CRC cells. Experimental results suggest that ω-3 PUFAs could increase the efficacy of radiotherapy and chemotherapy of CRC. CONCLUSIONS Lipid peroxidation, one factor of oxidative stress, might play a paramount role not only in carcinogenesis but also in potential therapeutic strategy on CRC. End products of lipid peroxidation, such as malondialdehyde, 4-hydroxy-2-nonenal, and isoprostanes, could be used as biomarkers for cancer detection, surveillance of treatment outcome and prognostic index for CRC patients. Furthermore, malondialdehyde and 4-hydroxy-2-nonenal have cytotoxic effect not only in normal cells but also in CRC cancer cells, which implies the potential role of PUFAs in CRC treatment.