Abstract Background American Indians (AI) in North Dakota present with higher rates of advanced-stage disease for screening detectable colorectal cancers and have lower overall baseline colorectal cancer screening rates than non-AIs. We sought to identify the perceived barriers and facilitators for the engagement with colorectal cancer prevention within North Dakota tribal communities. Methods Twelve semi-structured interviews were carried out across four tribal reservation communities in the state of North Dakota with American Indian adults between the ages of 30 and 75 years. We utilized purposive sampling to ensure maximum variation in age, sex, and tribal community until data saturation was achieved. The interviews were transcribed, and thematic analysis was carried out to identify consistent themes rooted within the data. Ethical approval was gained for this project from all relevant institutional review boards. Results Four main themes were identified as barriers for the engagement with colorectal cancer prevention, including: colorectal cancer screening barriers, focused on other health problems, lack of colorectal cancer tailored health promotion, and socio-cultural factors affecting colorectal cancer prevention. Three main themes were identified as facilitators for the engagement with colorectal cancer prevention, including: reasons for getting colorectal cancer screening, role of culture, and getting out into the community. Conclusion There is need for more community-rooted, strengths-based approaches to colorectal cancer prevention activities in AI communities in North Dakota. Socio-cultural factors, such as the use of storytelling, and the use of traditional knowledge have been demonstrated to be an important element of consideration for colorectal cancer tribal community engagement and prevention planning in the state.