Abstract Background Internet-based Cognitive Behavioural Therapy (iCBT) for the treatment of depressive disorders is innovative and promising. Various studies have demonstrated large effect sizes up to 2.27, but implementation in routine practice lags behind. Mental health therapists play a significant role in the uptake of internet-based interventions. Therefore, it is interesting to study factors that influence the therapists in whether they apply internet-based therapy or not. This study, as part of the European implementation project MasterMind, aims to identity the factors that promote or hinder therapists in the use of iCBT in depression care. Methods/Design The uptake of iCBT by therapists in routine mental health care practice for the treatment of depression will be evaluated by a mixed method approach, to provide an understanding of the implementation factors (quantitative), and to ascertain the facilitating and hindering factors in the involvement of therapists in the implementation of iCBT (qualitative). The involvement of therapists in the implementation of iCBT is analysed following the RE-AIM framework on the five dimensions Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance. This enables us to evaluate the reach of therapists, the impact of iCBT on depression care, the extent to which therapists adopt iCBT, the extent to which iCBT is delivered as intended, and how iCBT can be maintained over time. Discussion The results will provide valuable insight into the role of therapists in the implementation of iCBT for depression in secondary mental health care settings. They will result in concrete recommendations for how therapists can be facilitated in implementing and up-scaling iCBT for depression.