Background: Despite the need for hospice care as our society ages, adults in the U.S.’s southern rural region have limited awareness of hospice care. Objective: This study aims to assess the rate of awareness of hospice care among rural residents living in Alabama’s Black Belt region and examine social determinants of health (SDH) associated with the awareness. Methods: A cross-sectional survey was conducted among a convenience sample living in Alabama’s Black Belt region (N = 179, age = 18-91). Participants’ awareness of hospice care, demographic characteristics (ie, age and gender), and SDH (ie, financial resources strain, food insecurity, education and health literacy, social isolation, and interpersonal safety) were assessed. Lastly, a binary logistic regression was used to examine the association between SDH and hospice awareness among participants while controlling for demographic characteristics. Results: The majority of participants had heard of hospice care (n = 150, 82.1%), and older participants (50 years old or older) were more likely to report having heard of hospice care ( OR = 7.35, P < 0.05). Participants reporting worries about stable housing (OR = 0.05, P < 0.05) and higher social isolation were less likely to have heard of hospice care ( OR = 0.53, P < 0.05), while participants with higher health literacy had a higher likelihood to have heard of it ( OR = 2.60, P < 0.01). Conclusions: Our study is the first study assessing the status of hospice awareness among residents of Alabama’s Black Belt region. This study highlighted that factors including age and certain SDH (ie, housing status, health literacy, and social isolation) might be considered in the intervention to improve hospice awareness.