Abstract Purpose Black-White racial disparities have long been recognized in cancer incidence. National estimates may not reflect racial disparities in individual states. In Alabama (AL), a primarily rural underserved state, Black Americans are more often diagnosed with breast, prostate and colorectal cancer (CRC), with Black men more often diagnosed with lung cancer. Although rurality and area-level deprivation, as social determinants of health (SDoH), have been associated with cancer, their role in explaining racial disparities in cancer incidence remains unknown. We assessed racial disparities in breast, prostate, CRC and lung cancer incidence in AL. Methods We used the Alabama Statewide Cancer Registry (ASCR) to collect data on incident cases of breast, prostate, CRC and lung cancers diagnosed between January 1, 2010 and December 31, 2019. We categorized cases according to age group (0-14, 15-19, 20-24, 25-34, 35-44, 45-64, 65-84, ≥85 years), racial/ethnic group (non-Hispanic Black/White), rural-urban status (defined by AL Rural Health Association), and national area deprivation index (ADI) quartile (Q1-Q4) of census tract at diagnosis. For each combination of these variables, we calculated age-adjusted incidence per 100,000. We conducted bivariate descriptive analysis of incidence rates by race, and rural-urban status and ADI quartile stratified by race. Results Incidence of breast, prostate and CRC cancer was higher in Black versus White individuals (breast 143 vs 127; prostate 206 vs100; CRC males 57.2 vs 45.4, CRC females 42.7 vs 32.6). Lung cancer incidence was higher in Black males and White females (Black vs White: males 82.7 vs 77.6; females 36.9 vs 49.9). In all cancers, racial differences in incidence existed by rural versus urban status (breast Black 142 vs 144, breast White 131 vs 124; prostate Black 204 vs 207, prostate White 101 vs 99.4; male CRC Black 60 vs 55.3, male CRC White 47.7 vs 43, female CRC Black 43.5 vs 42.3, female CRC White 35.2 vs 30.2; male lung Black 84.5 vs 81.7, male lung White 85.1 vs 70.2, female lung Black 31.4 vs 40.1, female lung White 54.4 vs 45.6). In all cancers, racial differences in incidence also existed by ADI status (reporting Q1 vs Q4) [breast Black 190 vs 130, breast White 144 vs 118; prostate Black 269 vs 189, prostate White 109 vs 101; CRC male Black 64.2 vs 56.7, CRC male White 41.2 vs 49.7, CRC female Black 43.4 vs 43.5, CRC female White 29.5 vs 36.6; lung male Black 73.7 vs 91, lung male White 57.9 vs 97.6, lung female Black 41 vs 37.7, lung female White 40.8 vs 60.7]. Conclusions In AL, racial differences in incidence rates for each of the most common cancers exist overall and by key SDoH. Generally, Black individuals have higher rates of cancer, particularly those in rural and low ADI areas. Next, we will perform a decomposition analysis to decompose the Black/White differences in incidence into a portion explained and unexplained by rural-urban status and ADI. Ultimately, these results may inform interventions in a rural underserved state with a large Black population at higher risk of cancer. Citation Format: Mackenzie E. Fowler, Hayden Reeves, Melissa J. Smith, Geetanjali Saini, Mahak Bhargava, Ritu Aneja. Uncovering the role of social determinants of health in racial disparities in cancer incidence in Alabama [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A038.