Objective The aim of this study was to find if systemic family therapy (SFT) does work in anxiety and depression with epilepsy in adolescents (ADAE). Methods 104 adolescents with epilepsy, aged 13-20 years old, were included from December 2009 to December 2010, the enrolled patients were with anxiety [Hamilton Anxiety Scale (HAMA) score >= 14 points] or depression [Hamilton Depression Scale (HAMD) score >= 20 points]. The patients were randomly divided into the control group (n=52) treated with antiepileptic drugs (AED) and the intervention group (n=52) undergone Systemic Family Therapy (SFT) as well as AED. The AED improvements, anxiety and depression scores, Social Support Rating Scale (SSRS), Family Assessment Device (FAD) and scale of systemic family dynamics (SSFD) were observed after 3-month treatment. Results The frequencies of epileptic seizures in intervention group was decreased much more significantly than the control group (4.22 +/- 3.54 times/month vs. 6.20 +/- 5.86 times/month, p=0.04); and the scores of anxiety (9.52 +/- 6.28 points vs. 13.48 +/- 8.47 points, p=0.01) and depression (13.86 +/- 9.17 points vs. 18.89 +/- 8.73 points, p=0.02) were significantly decreased than the control group; meanwhile, the family dynamics and family functions were significantly improved, and the social support was also increased (p<0.05). Conclusion SFT combined with AEDs had better efficacies than AEDs alone, not only the frequency of epileptic seizures was decreased, but also the patients' anxiety and depression were improved, and the family dynamics, family functions and social support were improved.