Background: The high risk of resection surgery for hypothalamic hamartoma (HH) epilepsy drives interest in minimally invasive treatment. Stereo-electroencephalography-guided three-dimensional radiofrequency thermocoagulation (SEEG-3D RFTC) offers an alternative option. We investigated this technology's efficacy, safety, and prognostic risk factors. Methods: Patients with HH who underwent SEEG-3D RFTC were retrospectively analyzed. A high-density focal stereo-array electrode implantation was adopted. SEEG-3D RFTC was performed between two contiguous contacts of the same electrode or adjacent contacts of different electrodes. Outcomes were separately evaluated for clinical seizures, gelastic seizures (GS), and non-gelastic seizures (nGS). Kaplan-Meier survival analysis was used to assess treatment effectiveness. Risk factors were analyzed using log-rank tests and Cox regression analyses. Results: Sixty-nine patients were enrolled. The mean follow-up was 41.00 +/- 18.19 months. Seizure freedom was obtained by 48/69 (69.57%) patients for clinical seizures, 50/62 (80.65%) patients for GS, and 41/54 (75.93%) patients for nGS. Surgical procedures were well tolerated. In this study, the proportion of patients experiencing long-term complications was 10.14%. The percentages of HH ablation (p = 0.003; hazard ratio 0.956, 95% confidence interval 0.928-0.985) and HH attachment ablation (p = 0.001; hazard ratio 0.931, 95% confidence interval 0.892-0.970) were significantly associated with seizure outcomes. Conclusions: Optimized SEEG-3D RFTC is an effective and safe option for HH-related epilepsy and is especially suitable for use where laser interstitial thermal therapy is unavailable. Complete ablation of the HH and attachment site is essential for good outcomes.