Background and Objective: Health education in secondary school plays a critical role in anticipating hemoglobinopathies transmission risks. Nonetheless, there are only a few research studies examining the health literacy level of adolescents under age 19. The Objective of our study is to explore the knowledge and skills related to the prevention of hemoglobinopathies. Methods: A cross-sectional investigation was conducted among Tunisian youths attending public secondary schools and learning about human genetics (n = 356; male 28.1 %, female 71.9 %). Results: The Results show that concerning literacy to hemoglobinopathies, significant differences in knowledge, risk perception, and behavioral attitudes were found by gender, age, and school level (Sig < 0.05). 65,4 % has not identified the hereditary nature of diseases and confuse it with dietary iron anemia 41,6 %. Although 55,3 % of respondents recognized severe anemia as a symptom, however, 71,3 % did not link jaundice to thalassemia, almost 30% said this disease causes rash, fever, dry cough and sore throat. The Results show low levels the difficulties of youths to consider the hereditary transmission risks of haemoglobinopathies and to understand the importance of screening and genetic counseling. 36,8% of students (59% Male vs 28 % Female) do not consider it necessary to inform their partner of their carrier status. 59.5 % (67% Male vs 56.64 Female; Sig = 0.04) do not see the benefit of genetic counseling and prenatal diagnosis even if the family of one of the two partners has a history with disease. Conclusions: Knowledge acquisition in human genetics remains insufficient to actively engage adolescents in the primary prevention of hemoglobinopathies. It is essential to plan health promotion and education interventions in conjunction with genetic learning. Messages based on real-life stories can help in understanding these diseases and promote health literacy.