Background: Patient knowledge of palliative care (PC) has been demonstrated to improve the quality of end-of-life care. Current evidence indicates decreased knowledge of PC and decreased utilization of services such as hospice and advanced directives among Latinos in the US. Hispanic Americans make up 18.9 % of the US population, however, categories of Latino and Hispanic are broad and encompass different ethnic groups, each with unique cultures and experiences. Previous research has demonstrated different ethnicities have differing perspectives on end-of-life care. In this study, we aim to investigate variations in knowledge of PC between different Latino ethnic subgroups in the US. Methods: We employed data from the National Cancer Institute’s Health Information National Trends Survey (HINTS5–Cycle 2; 2018) for a nationally-representative sample of 3,504 adults (aged ≥18 years). Lack of knowledge of PC was assessed by respondents’ selecting “I’ve never heard of it” when asked, “How would you describe your level of knowledge about palliative care?” We performed a binomial regression assessing knowledge of PC and comparing this answer choice between Hispanic and non-Hispanic respondents as well as a Wilcoxon-Mann-Whitney test to compare among Hispanic subgroups. Results: Of all 3,504 survey respondents, 13.07% self-identified as Hispanic, and 65.2% stated they had never heard of palliative care. In the ethnic subgroups analyzed, 173 (79.4%) Mexicans, 33 (71.7%) Puerto Ricans, and 11 (55%) Cubans reported they had never heard of PC compared to 689 (62.2%) of non-Hispanics. We used a binomial regression to compare this response in Hispanics vs. non-Hispanics and found a significant difference in PC knowledge between Hispanics and non-Hispanics (p < 0.001), with an OR of 0.469 between the lack of PC knowledge answer choice and selecting Hispanic (95% CI 0.37-0.6). A Wilcoxon-Mann-Whitney comparing PC knowledge by subgroups found a significant difference between non-Hispanics and Mexicans (p< 0.001) but no differences between Hispanic sub-groups. Conclusions: Hispanics had lower levels of knowledge of PC than non-Hispanics. When stratified by Hispanic subgroups, only Mexicans had significantly lower PC knowledge than non-Hispanics. This calls for further research into why this ethnic group has lower knowledge of PC and what potential moderating factors could affect this association. Additionally, we need more studies on US Hispanics’ level of PC knowledge to assess if the trends seen between Hispanic subgroups in this survey are replicated.