This study examined the relationships of food insecurity, chronic diseases, and QoL in a U.S. sample of 630 deaf adults (18 to 89 years old; 55% female) who used American Sign Language (ASL). Measures of USDA Food Security Module, self-reported diagnoses of chronic diseases, and QoL were administered in ASL and English. Approximately 22% reported facing food insecurity, with low food security (11%) and very low food security (11.4%). QoL, but not the presence of chronic diseases, was significantly associated with food insecurity. Higher income and absence of depression acted as protective factors, reducing the risk for food insecurity.