Introduction Deep brain stimulation (DBS) of bilateral anteromedial subthalamic nucleus (amSTN) has been found to be helpful in a subset of patients with severe, chronic and treatment-refractory obsessive–compulsive disorder (OCD). Biomarkers may aid in patient selection and optimisation of this invasive treatment. In this trial, we intend to evaluate neurocognitive function related to STN and related biosignatures as potential biomarkers for STN DBS in OCD. Methods and analysis Twenty-four subjects with treatment-refractory OCD will undergo open-label STN DBS. Structural/functional imaging, electrophysiological recording and neurocognitive assessment would be performed at baseline. The subjects would undergo a structured clinical assessment for 12 months postsurgery. A group of 24 healthy volunteers and 24 subjects with treatment-refractory OCD who receive treatment as usual would be recruited for comparison of biomarkers and treatment response, respectively. Baseline biomarkers would be evaluated as predictors of clinical response. Neuroadaptive changes would be studied through a reassessment of neurocognitive functioning, imaging and electrophysiological activity post DBS. Ethics and dissemination The protocol has been approved by the National Institute of Mental Health and Neurosciences Ethics Committee. The study findings will be disseminated through peer-reviewed scientific journals and scientific meetings.