IntroductionThe EMPACOL Project aims to investigate the link between healthcare professionals’ (HCPs) empathy and the results of the curative treatment of non-metastatic colorectal cancer (CRC).Methods and analysisEMPACOL will be an observational multicentric prospective longitudinal study. It will cover eight centres comprising patients with non-metastatic CRC, uncomplicated at diagnosis in two French areas covered by a cancer register over a 2-year period. As estimated by the two cancer registries, during the 2-year inclusion period, the number of cases of non-metastatic CRCs was approximately 480. With an estimated participation rate of about 50%, we expect around 250 patients will be included in this study. Based on the curative strategy, patients will be divided into three groups: group 1 (surgery alone), group 2 (surgery and adjuvant chemotherapy) and group 3 (neo-adjuvant therapy, surgery and adjuvant chemotherapy). The relationship between HCPs’ empathy at the time of announcement and at the end of the strategy, quality of life (QoL) 1 year after the end of treatment and oncological outcomes after 5 years will be investigated. HCPs’ empathy and QoL will be assessed using the patient-reported questionnaires, Consultation and Relational Empathy and European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire, respectively. A relationship between HCPs’ empathy and early outcomes, particularly digestive and genitourinary sequelae, will also be studied for each treatment group. Post-treatment complications will be assessed using the Clavien-Dindo classification. Patients’ anxiety and depression will also be assessed using the Hospital Anxiety and Depression Scale questionnaire.Ethics and disseminationThe Institutional Review Board of the University Hospital of Caen and the Ethics Committee (ID RCB: 2022-A00628-35) have approved the study. Patients will be required to provide oral consent for participation. Results of this study will be disseminated by publication in peer-reviewed journals.Trial registration numberNCT05447611.