High health literacy (HL) plays a critical role in preventing or delaying the onset of cardiovascular diseases (CVDs) and can improve disease management and control. The present study aims to determine the association between HL and non-laboratory-based (office-based) Framingham 10-year risk score of CVD. This cross-sectional study was conducted on 648 people aged 30-65 in the health centers of Jahrom. The Health Literacy Instrument for Adults (HELIA) was used to assess HL. The non-laboratory-based Framingham risk score (FRS) was utilized to determine the 10-year risk of CVDs. Risk factors such as age, gender, diabetes, current smoking status, systolic blood pressure (SBP), hypertension (HTN) treatment, and body mass index (BMI) were applied in the non-laboratory-based model. The average age of the subjects was 44.7 ± 10.5 years, among which 49.2% were males. The prevalence of diabetes, HTN, and smoking equaled 8.5%, 15.7%, and 10%, respectively. In addition, the average BMI was 26.1 ± 3.6 kg/m2. Based on the non-laboratory-based Framingham 10-year risk score of CVD, 72.5%, 13.9%, and 13.6% of the subjects were in the low, moderate, and high risk groups, respectively. Based on the HL grouping, the levels of insufficient, borderline, sufficient, and excellent HL were 19.3%, 26.4%, 34.6%, and 19.7%, respectively. A significant association was observed between 10-year CVD risk and HL grouping. In addition, a negative correlation was reported at the individual level between HL and non-laboratory-based FRS among the whole population (r = - 0.39, p < 0.001), men (r = - 0.32, p < 0.001), and women (r = - 0.42, p < 0.001). A higher HL score is associated with a lower risk of CVD. In addition, the adjusted logistic regression analysis showed that there was a strong association between elevated CVD risk (≥ 10%) and HL (OR 6.1, 95% CI 2.9-12.6) among inadequate HL participants compared with excellent HL individuals. Thus, designing and implementing training programs to increase HL, especially among those who are at risk of CVDs, should be regarded as an important issue for the prevention of such diseases.