Abstract Allostatic load (AL) a measure of the cumulative physiological stress occurs when external stressors exceed an individual's ability to adapt, increasing the risk of chronic diseases, including cancer. In the United States (US), Hispanic/Latinx people face acculturation-related stressors like family separation, low socioeconomic status, language barriers, racism, and discrimination, which can elevate AL and cancer risk. This study aims to examine the moderating role of US citizenship status and length of time living in US on the relationship between high allostatic load and risk of cancer mortality among Hispanic/Latinx people. We performed a retrospective analysis using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010 among 7,299 Hispanic/Latinx people linked with National Death Index with follow-up through December 31, 2019. We defined high AL as having more than three abnormal measures among the following nine biomarkers: body mass index, C-reactive protein, diastolic blood pressure, glycated hemoglobin, systolic blood pressure, total cholesterol, serum triglycerides, and serum creatinine (above the 75th percentile), or serum albumin (below the 25th percentile). We compared differences in participant characteristics using Rao-Scott Chi-Square tests for weighted survey data. We fit weighted Cox proportional hazards models to estimate hazard ratios and associated 95% confidence intervals of cancer death, stratified by US residence and length of time in US Among 7,299 Hispanic/Latinx people, 2,835 (33.4% weighted) had high AL, and 4,464 (66.6% weighted) had low AL. Hispanic/Latinx people with high AL were more likely to be male, aged 40-59, have a lower level of formal education (52.0% vs. 43.6%, p- value <0.001), and were more often surveyed during the 2007-2010 NHANES period (43.2% vs. 37.2%, p-value <0.001) compared to those with low AL. When considering US residency, participants with high AL were more likely to live in the US longer than 15 years (38.2% vs. 24.8%, p-value <0.001) and be US citizens (65.0% vs. 54.7%, p-value <0.001). Regarding health behaviors, participants with high AL were less likely to have been diagnosed with heart attack and less likely to have any history of smoking. We observed that among Hispanic/Latinx people, those with high AL have a 97% increased risk of dying from any cancer (HR = 1.97, 95% CI = 1.24 - 1.34) when compared to those with low AL. When stratifying by US citizenship status, among Hispanic/Latinx US citizen population those with high AL have a 2.3-times higher risk of cancer death when compared to those with low AL (HR = 2.30, 95% CI = 1.22 - 4.32). Among those who are Hispanic/Latinx non-US citizens, those with high AL have 48% increased risk of cancer death compared to those with low AL, though non-significant (HR = 1.48, 95% CI = 0.64 - 3.43). Our preliminary findings highlight that Hispanic/Latinx people with US citizenship who experience high levels of chronic stress, as measured by AL, have an increased risk of cancer mortality. Citation Format: Jessica Amezcua, Mellisa Lopez-Pentecost, Jessica Y. Islam, Marlo Vernon, Kathleen L. O'Connor, Justin X. Moore. Effect modification of United States residency and length of time in US on the relationship between allostatic load and cancer mortality risk in Hispanic/Latinx Americans: Insights from NHANES (1999-2019) [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 B154.