Abstract Objective: Assess consumer experience and health impact among under-resourced individuals who were enrolled into longitudinal navigation to address social determinants of health (SDOH) needs and health goals related to cancer primary and secondary prevention. Background: The Yale Cancer Disparities Firewall Project is a multi-tiered initiative to address the social determinants of health (SDOH) and other challenges that prevent at-risk communities from receiving the full benefit of the many available cancer prevention and cancer screening options. A community-facing health navigation program, staffed by community members who have received extensive multidisciplinary training is a central component of this program. Methods: Of the 61 currently enrolled individuals (all of whom are either African American/Black or Hispanic/Latinx), we collected questionnaire data from 24 individuals (39% response rate). In general, participants are enrolled for a minimum of 1 year, but most have been followed for 2 years. Respondents were similar to non-respondents with respect to race (60% were Black/African American vs 61.2%, respectively) and age (mean = 44.8 vs 47.2 years, respectively). Respondents were more likely to be female (85% vs 71.4%, p =.009), Hispanic/Latinx (35% vs 42%), but significantly less likely to be foreign-born (15% vs 26.5 %, p = .021). We assessed satisfaction with assigned navigator(s), uptake of referred services, knowledge gained, health behavior change, and self-rated health (SRH). Results: Per self-report, 79.2% of participants agreed and a further 12.5% somewhat agreed that they were overall satisfied with their experience with the health navigation program. Importantly, two-thirds (66.7%) agreed and a further 20.8% somewhat agreed that they changed their behavior to improve their health and well-being because of the program. Of the 5 health focused services offered, the most commonly reported uptake was physical activity (87.5%), followed by learning how to eat healthier and losing weight. Additionally, one third (33.3%) of participants received assistance with reducing or stopping smoking. In terms of secondary prevention, 62.5% of clients received assistance with cancer screening. Of the 5 SDOH focused services offered, the most common was assistance with finding food to eat (66.7%) followed by assistance with paying utilities (45.8%), a shift from the priority needs at baseline (40% needing food assistance, and 35% with housing concerns), presumably reflecting the additional strains associated with the COVID-19 pandemic. Conclusions: Against the backdrop of COVID-19, these findings suggest that addressing SDOH barriers through individual navigation is an important add-on service when facilitating access to services to maintain healthy lifestyle and adhere to cancer screening guidelines. Although this was a pilot program, we foresee the opportunity to utilize trained non-clinical navigators and/or community health workers and to promote cancer prevention in at risk communities. Citation Format: Monique K. Stefanou, Sakinah C. Suttiratana, Denise Stevens, Eduardo Reyes, Jonathan Colon, Eiman Ibrahim, Roy L. Herbst, Beth A. Jones. Impact of health navigation program on healthy lifestyle and cancer screening in population with significant social determinants of health (SDOH) barriers [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-264.