Background The Basque Health Service (Spain) approved the Colorectal Cancer (CRC) screening programme in 2008; targeted at residents (50 to 69 years old) by biennial faecal immunochemical test and colonoscopy in positive cases. Total coverage was reached in 2014. Despite our high participation rate (72.3%), some people have never been screened, probably due to several factors (socio-economic factors, lifestyles, comorbidities, health preventive actions, etc.). The identification of these factors could be crucial in order to improve the results and impact of the programme. Methods Cross sectional descriptive study. All invited population in a complete round between 2015 and the first trimester of 2017 were included. Data base was linked to registered health risk factors, preventive activities managed by Primary Care and socioeconomic deprivation index. Univariate and multivariate analyses were performed by SPSS 23.0. Results 515,388 people were invited and 71.9% participated. Non-participation is significantly (p ≤ 0.001) related to: being men (OR = 1.10); younger than 60 (OR = 1.18); smoker (OR = 1.20); hypertensive (OR = 1.14) and diabetic (OR = 1.40), as well as to having a severe comorbidity (OR = 2.09) and very high deprivation (OR = 1.15). Low use of Primary Care services (OR = 2.39) and inappropriate control of risk factors also increase the likelihood of not participating. Conclusions Several factors addressed in Primary Care influence the participation in the CRC Screening Programme. Its results and impact (decreasing incidence and mortality) could be improved if individual and socioeconomic factors are taken into account to increase participation. Primary care and social networks are key in further planned interventions. Key messages Decreasing inequalities in the screening participation is one of the most important objectives in this Public Health strategy. Primary Care plays a key role in all the screening programmes’ implementations.