Abstract Background Alcohol Use Disorder is a severe mental disorder affecting the individuals concerned, their family and friends and society as a whole. Despite its high prevalence, novel treatment options remain rather limited. Two innovative interventions used for treating severe disorders are the use of real-time functional magnetic resonance imaging neurofeedback that targets brain regions related to the disorder, and mindfulness-based treatments. In the context of the TRR SFB 265 C04 “Mindfulness-based relapse prevention as an addition to rtfMRI NFB intervention for patients with Alcohol Use Disorder (MiND)” study, both interventions will be combined to a state-of-the art intervention that will use mindfulness-based relapse prevention to improve the efficacy of a real-time neurofeedback intervention targeting the ventral striatum, which is a brain region centrally involved in cue-reactivity to alcohol-related stimuli. Methods/design After inclusion, N = 88 patients will be randomly assigned to one of four groups. Two of those groups will receive mindfulness-based relapse prevention. All groups will receive two fMRI sessions and three real-time neurofeedback sessions in a double-blind manner and will regulate either the ventral striatum or the auditory cortex as a control region. Two groups will additionally receive five sessions of mindfulness-based relapse prevention prior to the neurofeedback intervention. After the last fMRI session, the participants will be followed-up monthly for a period of 3 months for an assessment of the relapse rate and clinical effects of the intervention. Discussion The results of this study will give further insights into the efficacy of real-time functional magnetic resonance imaging neurofeedback interventions for the treatment of Alcohol Use Disorder. Additionally, the study will provide further insight on neurobiological changes in the brain caused by the neurofeedback intervention as well as by the mindfulness-based relapse prevention. The outcome might be useful to develop new treatment approaches targeting mechanisms of Alcohol Use Disorder with the goal to reduce relapse rates after discharge from the hospital. Trial registration This trial is pre-registered at clinicaltrials.gov (trial identifier: NCT04366505; WHO Universal Trial Number (UTN): U1111–1250-2964). Registered 30 March 2020, published 29 April 2020.