Purpose The high risk of resection surgery for drug-resistant insular epilepsy has driven interest in new treatment techniques. Stereo-electroencephalography-guided three-dimensional radiofrequency thermocoagulation (SEEG-3D RFTC) offers an alternative option. Herein, we present the detailed protocol and investigation of the efficacy and safety of a preliminary observational study. Methods From February 2017 to April 2021, ten patients diagnosed with insular epilepsy were enrolled in the study. They underwent implantation of a combination of SEEG electrodes to form a high-density focal stereo-array in insula, including oblique electrodes through the long axis of insula and orthogonal electrodes to widely cover the medial and lateral insula. SEEG-3D RFTC was performed between two contiguous contacts of the same electrode, or between two adjacent contacts of different electrodes. Results Surgical procedures were well tolerated, with no related long-term complications. Seizure-free outcome was achieved in seven patients (70%), including ILAE I in four and ILAE II in three. Two other (20%) patients had rare seizures (ILAE III). One (10%) patient experienced an ILAE IV outcome (follow-up = 12--63 months). The responder rate (including ILAE I-IV) was 100%. Conclusion The optimized SEEG-3D RFTC is an effective and safe option for the treatment of drug-resistant insular epilepsy.