"Abstract Introduction: American Indian and Alaska Native populations face persistent disparities in cancer incidence, mortality, and screening. In the Zuni Pueblo, health inequities persist for cancer screening rates, including cervical, breast, and colorectal cancer screening rates. This study evaluates the impact of a culturally tailored, community-based, cognitive-behavioral education intervention aimed at improving cancer-related knowledge, attitudes, and screening behaviors among Zuni adults. Methods: A mixed-methods, community-engaged study was conducted with 117 Zuni adults (aged 21-75) who were nonadherent to United States Preventive Services Task Force cancer screening guidelines. Participants completed pre- and postintervention surveys and engaged in age- and sex-specific cancer education sessions focused on cervical, breast, and/or colorectal cancer. Quantitative data were analyzed to assess changes in screening behavior and attitudes. Qualitative data from three post-intervention focus groups and two in-depth interviews (n = 12) were analyzed thematically to explore participant experiences and perceptions of the intervention. Results: Post-intervention, screening attempts increased for all groups: 75% of younger women for cervical cancer, 60% of older women for mammograms, and 43% of men and 56% of women for stool blood tests. Participants reported higher odds of discussing their personal cancer risk with family, OR (95% CI) = 1.23 (1.12, 1.35), including significant associations for younger women and men. Qualitative participants emphasized the value of culturally specific content, visual materials, and social support in motivating screening. Barriers included limited appointment availability, transportation challenges, and concerns about confidentiality. Conclusions: This culturally tailored education intervention enhanced cancer screening knowledge, attitudes, and behavior among Zuni Pueblo adults. Community engagement and culturally congruent messaging were essential to program success. Future efforts to reduce cancer disparities in indigenous communities should integrate Tribal perspectives, address structural barriers, and build sustainable, local capacity for cancer prevention and screening."