INTRODUCTION: Despite a substantial number of studies providing evidence for the efficacy of psychological treatment for mild-to-moderate depression, maximally only 50% of participants respond to treatment, even when using gold-standard treatments such as cognitive-behavioural therapy (CBT) and interpersonal therapy. New approaches such as the 'third wave' psychotherapies have provided promising results; however, studies concerning the comparison with evidence-based treatments are lacking. This study aims to compare the efficacy of clinical hypnotherapy (HT) with gold-standard psychotherapy (CBT) in the treatment of mild-to-moderate major depressive episodes.METHODS AND ANALYSIS: The present study comprises a monocentric, two-armed, randomised-controlled, rater-blind (non-inferiority) clinical trial. A total of 160 participants with mild-to-moderate major depression episode will be randomly assigned to either CBT or HT involving 20 sessions of psychotherapy over a period of 24 weeks. We predict that the average improvement in the Montgomery-├ůsberg Depression Rating Scale score will not be inferior in HT compared with CBT (non-inferiority hypothesis).Further outcome parameters will include the number of participants responding to treatment following the completion of treatment and 1?year after. Additionally, quality of life, treatment expectations and hypnotic susceptibility before and after end of treatment will be assessed.ETHICS AND DISSEMINATION: The study protocol and the documents for the informed consent have been approved by the Ethics Committee of the University Hospital Tuebingen (061/2015B02). The results of this trial will be submitted for publication in peer-reviewed journals, and will be presented at national and international conferences.TRIAL REGISTRATION NUMBER: NCT02375308; Pre-results.