Objective Previous studies have shown that having promotion-oriented goals (e.g. wanting to become healthy) or prevention-oriented goals (e.g. wanting to avoid getting ill) can affect people's health-related decisions and behaviour by emphasising aspects and information that seem relevant in light of what they want to achieve. However, this issue has not yet been researched regarding colorectal cancer (CRC) screening. With our study, we aimed to examine the relationship between people's goal-orientation or focus on advantages or disadvantages and their CRC screening participation, as this could provide insights for supporting people in making this complex decision. Methods An online survey was carried out among a sample of first-time CRC screening invitees (1282 respondents, response rate 49%). We assessed people's goal-orientation (i.e. promotion- orientation and prevention-orientation), focus on the advantages or disadvantages of CRC screening, screening participation and main considerations (e.g. cancer is a serious illness) concerning their screening decision. Results Generally, CRC screening participants scored higher on both promotion-orientation and prevention- orientation than non-participants. Both CRC screening participation and non-participation were not associated with a dominant goal-orientation. CRC screening participants did show a dominant focus on the advantages of CRC screening. Mediation analysis showed support for our premise that the relationship between people's goal-orientation or focus on advantages or disadvantages and their screening participation could be (partially) mediated by people's main considerations concerning CRC screening. Conclusion CRC screening participants and non-participants differed in their goal-orientation and focus on advantages or disadvantages. CRC screening participation appears to be associated with a focus on the advantages of CRC screening, which could impede the making of an informed decision. CRC screening non-participation appears not to be associated with any clear goal-orientation or focus, or we have not yet managed to capture this, which could be either beneficial or problematic for making an informed decision.