Abstract The incidence of hepatocellular cancer (HCC) in the Bronx is 61% higher than the rest of New York State. Underserved populations are not well represented in clinical trials of immune checkpoint inhibitors. The purpose of this study is to analyze the efficacy of immunotherapy treatment in a diverse and underserved patient population in the Bronx. Study demographics include 194 patients treated with ICI at the Montefiore Einstein Comprehensive Cancer Center (MECCC) between 2017 and 2022. A retrospective electronic medical record (EMR) review was conducted of all adult patients and this sample size was identified as having advanced HCC treated with immunotherapy. Outcome parameters such as overall survival and disease control rate assessed by radiologists using the Modified Response Evaluation Criteria in Solid Tumors (mRECIST 1.1) were reported. Survival was evaluated using parameters such as baseline serum alpha-fetaprotein(AFP) level, its evolution at the 3-month re-evaluation mark, the Child-Pugh(CP) class and MELD-Na score at the time of diagnosis. Categorical variables were analyzed by Chi-squared test and survival was analyzed using Kaplan-Meier (KM) curves. MECCC patients were 40.7% Hispanic and 20.6% Black, compared with 3% and 2% respectively in the landmark IMbrave 150 study. Median overall survival (mOS) on ICI was 9.0 months, 25.0 months for the 100 (51.5%) favorable-prognosis Child Pugh A (CPA) patients included in HCC clinical trials. Disease control rate (DCR) was 58.5% among 123 evaluable patients per mRECIST 1.1. Baseline liver function, as defined by CP and Model for End Stage Liver Disease-Sodium (MELD-Na), correlated with survival (p<0.001). Hepatitis C Virus (HCV) and alcoholism were over-represented relative to National Cancer Institute (NCI) data (56.2% vs 4.7% and 38.7% vs 8.2%, respectively). HCV treatment correlated with prolonged survival in infected patients (p=0.0017). AFP decline correlated with response (p=0.001). Hispanic patients lived longer when clinical variables were controlled for (mOS 52 vs 23 months; p=0.011). In summary, our patient population differed significantly in racial composition and etiology of liver disease from clinical trial populations on which ICI was tested. In an underserved HCC population, ICI yielded a DCR of 58.5% and low rates of severe toxicity. This work highlights ICI efficacy in minority groups, a need for earlier HCC diagnosis and for studies of genetics and environmental factors in Hispanics with HCC. Citation Format: Fernand Bteich, Lydia Bioh, Kush Desai, Chenxin Zhang, Anahat Kaur, Rahel A. Levy, Aaron Wang, Sharmin Sultana, Andreas Kaubisch, Milan M. Kinkhabwala, Sarah Bellemare, Shabnam A. Fidvi, Devaraju Kanmaniraja, Robert G. Berkenblit, Jee-Young Moon, Adebola A. Adedimeji, Clara Y. Tow, Yvonne M. Saenger. Immunotherapy efficacy in advanced hepatocellular carcinoma in a diverse and underserved population in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3722.