Abstract Background: In the US, food insecurity is a public health issue and can have a negative impact on the health and well-being of adult populations including those who have cancers. Data on food insecurity among lesbian, gay, bisexual, or other sexual minority (LGB+) adults with cancers (AWCs) is lacking. Further, disparities in food insecurity across LGB+ and racial/ethnic minority AWCs at the national level are not clear. Methods: We conducted a secondary analysis of publicly available data from the 2021 National Health Interview Survey that used stratified clustering sampling to interview US adults aged ≥18 years. We further limited the analysis to adults who 1) had a cancer diagnosis, 2) reported sex assigned at birth, and 3) self-identified as either straight/heterosexual or LGB+. Food insecurity, measured using a 10-item questionnaire assessing household food situations in the past 30 days, was dichotomized as “yes/no.” Weighted proportions and 95% confidence intervals (CI) were calculated and compared using Rao-Scott chi-square tests. Multivariable logistic regression was used to compute adjusted odds ratios (aOR [95% CI]) and examine differences in food insecurity by race/ethnicity and sexual orientation. All analyses accounted for complex survey design. Results: We obtained an unweighted sample of 3,517 (weighted sample 23,747,209) AWCs. The mean age was 65.4 years; 3.1% were self-identified as LGB+; 83.5% were White, 6.5% were Black, and 6.3% were Hispanic. Overall, 4.7% (95% CI: 3.8–5.6%) experienced food insecurity. LGB+ AWCs reported a higher proportion of having experienced food insecurity than heterosexual AWCs (14.7% [95% CI: 6.4–23.0%] vs. 4.4% [95% CI: 3.5–5.3%], p<.0001). Among female AWCs, LGB+ AWCs were more likely than heterosexual AWCs to have experienced food insecurity (20.1% [95% CI: 7.7–32.5%] vs. 5.2% [95% CI: 4.0–6.4%], p<.0001). Compared with White AWCs (3.8%, 95% CI: 2.9–4.7%), Black (10.0%, 95% CI: 5.1–15.0%) and Hispanic (9.7%, 95% CI: 5.4–14.1%) AWCs reported higher proportions of having experienced food insecurity (p<.0001). In the adjusted regression model, LGB+ AWCs had higher odds of food insecurity than heterosexual AWCs, though the difference was not statistically significant (aOR=2.01, 95% CI: 0.74–5.48). Black AWCs had higher odds of food insecurity than White AWCs (aOR=2.24, 95% CI: 1.15–4.36). AWCs on Medicaid/Medicare had greater odds of food insecurity than those privately insured (aOR=2.54, 95% CI: 1.43–4.52). AWCs who were not employed also had greater odds of food insecurity than those employed (aOR=3.56, 95% CI: 1.87–6.77). Conclusions: In this national sample of US AWCs, the prevalence of food insecurity was higher in LGB+ and racial/ethnic minority groups. Black and Hispanic AWCs were more likely than their White counterparts to have experienced food insecurity. Our findings suggest the need for intervention programs and public policies addressing food insecurity among AWCs, particularly among those who are in LGB+, racial/ethnic minority, or socioeconomically disadvantaged communities. Citation Format: Jincong Q. Freeman, Xinyi Li, Yong Gun Lee. Prevalence of and disparities in food insecurity among racial/ethnic and sexual minority adults with cancers in the US: Analysis of the National Health Interview Survey [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B012.