Abstract As a component of statewide cancer needs assessment, this study explored factors impacting colorectal cancer (CRC) screening and approaches to increase screening among Native Americans of Nebraska. Three 75-minute focus groups were conducted October-December 2021: Omaha Urban Indian clinic (n=11), Lincoln Urban Indian clinic (n=6), and Ponca Tribe (n=9). Participants were Native American cancer survivors and caregivers aged 30+ residing in Nebraska. Verbatim transcripts were inductively coded and analyzed using a directed content analysis approach. Most participants were female (88%) and caregivers (85%). Most had heard of colonoscopies (83%), but awareness of fecal tests was low with two participants unaware of any screening. Only 38% had heard of the Fecal Occult Blood Test despite tribal outreach during March incentivizing stool tests. Reasons for low uptake of screening tests included lack of awareness (“What is colorectal cancer?” and “I don't think a lot of Natives get that type of cancer, do they?”), elderly avoidance of medical care (“even when I’m real sick I have to be…near…death” before seeking care), fear (“fearing what they’re gonna find out”), and embarrassment (“perception of manhood”). The invasive and uncomfortable procedural aspect of colonoscopy and use of excreta for stool-based tests "Because I don't wanna be digging in my poop" were other deterrents. Some providers did not strongly recommend the screening. Other barriers include insurance and transportation/travel distance for colonoscopy. Suggested approaches to improve CRC screening were increasing awareness of CRC and screening options using billboards, flyers, posters, brochures, health fairs, public meetings, and social media (e.g., Facebook). Posters and educational materials in clinics were already in use. Suggested message content should portray that CRC is treatable “if they catch it in time,” emphasizing being there for family (“you’ve got kids, you want to see them graduate”), funny (“goofy…they can kinda laugh at the ad and hopefully not be so nervous”) and having community members share CRC survival stories. Engaging the community was also discussed either through 1) having nursing students provide health education outreach, 2) forming elder committees to encourage the elderly to complete screenings, and/or 3) ensuring physicians recommend and explain the importance of screenings during appointments. Community support in terms of transportation, social workers to attend appointments with the elderly, and financial counselors were discussed as important to complete screenings. Certain types of health facilities should enhance their partnership with Native Americans to share information with the community. Low awareness and wrong perception of CRC and screening tests are reasons for low utilization of screening. Participants expressed a desire for the researchers to continue building relationships with the tribal groups to address CRC. The state can use study results to prioritize interventions to reduce cancer care disparities. Citation Format: Krishtee Napit, Kendra L. Ratnapradipa, Lady Beverly Luma, Danae Dinkel, Shinobu Watanabe-Galloway. Colorectal cancer screening among Native Americans of Nebraska: A qualitative analysis of the barriers and facilitators [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR003.