To investigate the safety and short-term efficacy of domestic magnetic resonance-guided laser interstitial thermotherapy (MRgLITT) in the treatment of drug-resistant epilepsy. Patients with drug-resistant epilepsy treated with a domestic MRgLITT system in the Department of Neurosurgery, Xuanwu Hospital, Capital Medical University from October 2020 to April 2021 were prospectively enrolled. The damage volume ratio was assessed immediately after surgery, and perioperative complications were recorded and followed up. The clinical safety and short-term efficacy were evaluated using the Engel classification. A total of 22 patients were included, including 12 males and 10 females, aged from 3 to 45 years old [(24±13) years]. There were 5 cases of medial temporal lobe epilepsy (MTLE), 3 cases of hypothalamic hamartoma (HH), 7 cases of focal cortical dysplasia (FCD), and 7 cases of other types, respectively. The mean operation time and blood loss was (173±49) min and (3.7±1.6) ml. The postoperative length of hospital stay was (5.5±1.8) days, and the average damage volume ratio was 92.6%. Among them, only 2 patients (FCD of the parietal lobe) showed transient contralateral limb weakness, without any serious complications such as symptomatic intracranial hemorrhage and cerebral infarction. The follow-up time was 14 to 168 days. There were 13 Engel class Ⅰ cases (59.1%), 2 Engel class Ⅱ cases (9.1%), 2 Engel class Ⅲ cases (9.1%) and 5 Engel class Ⅳ cases (22.7%), respectively. Short-term incident-free rates were MTLE 5/5and FCD4/7, respectively. Domestic MRgLITT system is stable, reliable and safe in the treatment of drug-refractory epilepsy, and has better short-term efficacy in MTLE and FCD patients.