To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (EpilcureTM, GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study.This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariate linear regression was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well.The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 (P <0.05). The average response rate after 13 months of treatment was 42%, with 21% (n = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 (β <0, P <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed.The preliminary findings suggest that EpilcureTM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required.Chinese Clinical Trial Registry (No. ChiCTR2200055247).Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.