Objective: The objective was to analyze the role of Health Literacy (HL) as a factor associated with tooth loss among users of the Brazilian Health System with chronic non-communicable diseases. Methods: The cross-sectional study was conducted with adult and elderly users at ten Family Health Clinics in the town of Piracicaba, São Paulo State, Brazil. A questionnaire was applied with sociodemographic (sex, age, skin color and education), behavioral (brushing and flossing), health determinants (dental health services) and clinical data (pain). Mouth conditions were collected by intraoral examination of visible dental biofilm and community Pediodontal Index. The systemic clinical conditions (blood glucose, glycated hemoglobin and blood pressure) were extracted from the medical records. The explanatory variable was HL (low, medium and high), measured with the Health Literacy Scale (HLS-14). Results: The outcome was tooth loss measured by the index of decayed, missing and filled teeth. Logistic regression was performed using a conceptual model for HL (p < 0.05). For the 238 subjects, the mean age was 62.7 years (± 10.55). Tooth loss was associated with HL in regression models adjusted by type of dental service, dental frequency, and dental floss. In the final model, the factors associated with tooth loss are older age (OR=1,12; 95%CI=1,07–1,17), a lower education (OR=3,43; 95%CI=1,17–10,10), irregular use of dental floss (OR=4,58; 95%CI=1.75–7,31), irregular use of dental services (OR=2,60; 95%CI=1,32-5,12), periodontal pocket (OR = 0,31; 95% CI 0,01–0,08), having visible dental biofilm (OR=7,23; 95%CI=3,19–16,41) and a higher level of blood sugar (OR=1,98; 95%CI=1.00–3,92). Conclusions: Tooth loss was associated with HL when adjusted by health behaviors; when sociodemographic variables and clinical conditions were included, it was less significant. In the final model, behaviors, determinants in health and clinical conditions were risk indicators of tooth loss, showing the multifactorial nature of this phenomenon.