OBJECTIVE: This study determined the mediating role of knowledge about epilepsy in the relationship between attitudes toward epilepsy and health literacy in Turkey. METHODS: This descriptive and cross-sectional study was conducted in Turkey with 4,393 participants. The sociodemographic form, Epilepsy Attitude Scale, Epilepsy Knowledge Scale, and Health Literacy Scale were used for data collection. RESULTS: The participants' mean attitude score was 57.05 ± 10.15, mean knowledge score was 7.70 ± 4.22, and mean health literacy score was 51.95 ± 9.61. Health literacy scores significantly predicted attitude (β = 0.498) and knowledge (β = 0.382) scores (p <
0.05). Knowledge scores significantly predicted attitude scores (β = 0.529
p <
0.05). However, health literacy (β = 0.346) and knowledge scores (β = 0.397) together significantly predicted attitude scores (p <
0.05). The knowledge score has a mediating role between health literacy and attitude score (β = 0.152
p <
0.05). CONCLUSION: Individuals had relatively positive attitudes toward epilepsy and moderate levels of knowledge and health literacy. Health literacy positively affected knowledge and attitude towards epilepsy. However, knowledge about epilepsy also positively affected attitude. Additionally, health literacy and knowledge of epilepsy together positively affected attitudes toward epilepsy. Knowledge about epilepsy mediated the relationship between health literacy and attitude toward epilepsy. In this context, it is recommended that programs to raise awareness and improve health literacy be organized, social sensitivity should be increased, and additional epilepsy research should be conducted.