Introduction and Objective.Colorectal cancer (CRC), a malignant neoplasm of the gastrointestinal tract, affects the colon and rectum, its incidence is high, being the third most common neoplasm in men, with two million cases/year and survival <70%/5 years. The pathophysiology and progression of CRC are closely related to endoplasmic reticulum stress (ERE) and the unfolded or misfolded protein response (UPR). ERE can be triggered by various oxidative stress and inflammation factors with high UPR load followed by physicochemical and conformational interactions. The aim of the review is to present recent evidence on the relationships between endoplasmic reticulum stress, unfolded protein response and colorectal cancer. Review Methods. An expanded integrative review was carried out of scientific information from PubMed, LILACS and SciELO health databases. Articles containing key words were selected for abstract fast readings, followed by full text selections of works containing targeted subjects. From a total of 198 articles, 96 were selected (92% ≤ 8 years) for inclusion in the review. Brief description of the state of knowledge. New developments in CRC research are presented within approaches to molecular pathophysiological pathways, a spectrum of therapeutic targets and suggestive diets with a view of intestinal microbiota and dysbiosis, considering progression stages and evidences correlating CRC to socio-environmental and innate or acquired genetic load. Putative CRC target compounds and drugs, such as Aspirin, Fucoidan, PERK inhibitor, antimicrobial and current natural antioxidants are briefly presented and discussed. Summary. Chaperone proteins may accumulate misfolded proteins in the endoplasmic reticulum, causing disruption of ERE proteostasis. While CRC progression is closely related to these signaling pathways, a better understanding is vital for new target-specific anticarcinogenic molecules.