Background <p>Patient portals integrated within electronic health records (EHRs) offer a scalable strategy to promote colorectal cancer (CRC) screening by providing access to education, appointment scheduling, screening reminders, and enhanced communication. However, little is known about how patients and personnel in Federally Qualified Health Centers (FQHCs) engage with these tools to support CRC prevention.</p> Methods <p>This convergent mixed-methods study assessed barriers, facilitators, and recommendations related to patient portal use and CRC screening promotion in three FQHCs in the Midwest. Surveys and semi-structured interviews were guided by the Consolidated Framework for Implementation Research (CFIR) and the Technology Acceptance Model (TAM). Eligible participants included patients aged 45–75 and personnel engaged in patient care or portal use.</p> Results <p>Seventeen patients and 17 personnel completed surveys and interviews. Most patients (74%) and personnel (71%) found the portal easy to use, and 79% of patients believed it would support cancer screening scheduling. Nearly all personnel (94%) supported portal implementation and were willing to promote CRC screening through it. Identified facilitators included accessible design, embedded education, and alignment with clinical workflows. Barriers included limited access, low digital literacy, and competing staff demands. Participants offered strategies to improve usability, promote culturally relevant content, and deliver preparatory education via the portal. Feedback on a digital CRC screening video suggested strong motivation to screen and support for future integration into portal workflows.</p> Conclusion <p>Patient portals are feasible and acceptable tools for increasing CRC screening in FQHCs. Implementation strategies addressing access, literacy, and content relevance are needed to optimize portal-based interventions.</p>