The link between self-regulation concepts, epilepsy and Quality of Life (QoL) remains inadequately investigated. We aimed to explore the extent to which epilepsy severity, gender, and self-regulation concepts (illness perceptions, autonomous treatment regulation, perceived autonomy support by parents) predict QoL in adolescents with epilepsy.Methods: Interviews using the KIDSCREEN-27 Questionnaire, the Brief Illness Perceptions Questionnaire, the Perceptions of Parents Scales and the Treatment Self-Regulation Questionnaire were conducted in 100 patients (M_age=13,9, SD=2.21, 41% girls). A multiple hierarchical regression analysis was performed.Results: Most patients (91%) were well controlled on antiepileptics; 3% had infrequent seizures; 6 % were pharmacoresistant. In model 1, gender predicted significantly QoL (R²=0.078, adjusted R²=0.069, F=8.32, df=1, P<0.010). Adding epilepsy severity (model 2: R²=0.117, adjusted R²=0.099, F=6.42, df=2, P<0.010), illness perceptions (model 3: R² =0.339, adjusted R²=0.281, F=5.83, df=8, P<0.001), autonomous treatment regulation (model 4: R²=0.378, adjusted R²=0.316, F=6.08, df=9, P<0.001), and patients' autonomy support (model 5: R² =0.423, adjusted R²=0.358, F=6.52, df=10, P<0.001), a significant increase in explained variance occurred.Conclusions: At a univariate level male gender, having less severe epilepsy, expecting less consequences from epilepsy, believing that the epilepsy will not last long, freedom, from symptom, being less concerned about epilepsy, the feeling of having more personal control over the disease and less treatment control, regulating less autonomously the treatment and perceiving more autonomy support by parents were significantly associated with better QoL. However, at a multivariate level it appeared that less concern, less autonomous treatment regulation and more autonomy support result in better QoL.