Introduction: This investigation evaluates the effectiveness and safety of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) as a treatment modality for drug-resistant epilepsy. Material and methods: A retrospective review of clinical data from 40 paediatric patients with drug-resistant epilepsy, who underwent SEEG-guided RF-TC at our Epilepsy Center between 2020 and 2022, was conducted. This review included the patients' medical history, imaging and electroencephalography results, surgical procedures, and follow-up outcomes. Results: The duration of SEEG monitoring, accompanied by concurrent electrical stimulation tests, varied from 3 days to 4 weeks. Following RF-TC surgery, 4 patients demonstrated temporary neurological impairments, including central facial and tongue weakness, reduced limb strength, and challenges in fine motor hand movements. All these symptoms were related to lesions in the central region, but showed improvement within 2 weeks to 3 months post-surgery. There were no reported instances of status epilepticus, intracranial haemorrhage, or infections. During a follow-up period of 6 months to 2.5 years, seizure control was achieved in 25 patients (62.5%) at 6 months post-surgery, and a > 50% decrease in seizure frequency was observed in 10 patients. In 5 patients where seizure control was not achieved, the management of epilepsy seemed to be independent of factors such as age at surgery, duration of preoperative disease, seizure type, or negative MRI findings (p > 0.05). Patients with controlled epilepsy exhibited cognitive improvement, with some demonstrating no EEG abnormalities upon follow-up and a decrease in antiepileptic medication. Conclusions: SEEG-guided RF-TC appears to be a potentially effective and safe therapeutic approach for paediatric patients with drug-resistant epilepsy.