Epilepsy is a severe health disorder affecting people of all ages with high prevalence worldwide. The introduction of new antiepileptic drugs has yielded notable effects in recent decades, yet there are still approximately 30% of patients with seizures refractory to medical therapy. Open surgical resection is widely accepted as a highly effective approach for the treatment of drug-resistant focal epilepsy if the epileptogenic zone can be precisely delineated. However, concerns about the impact of open surgery on brain function have driven considerable interest in less invasive techniques. Clinically, stereoelectroencephalography (SEEG) offers a unique means of exploring the pathophysiologic process and accurately mapping the epileptogenic network in presurgical evaluations for patients with epilepsy because of insufficient information from other noninvasive investigations. Moreover, SEEG-guided radiofrequency thermocoagulation (SEEG-guided RF-TC), which ablates lesions directly through the recording electrodes according to electroclinical evidence, has emerged as a promising, minimally invasive modality with notable preservation of neurocognitive functions. This critical review summarizes the technical details of the parameters and the selection of patients for SEEG-guided RF-TC based on the literature as well as our experiences. With respect to the parameters, the power and duration of RF-TC are discussed. In particular, an optimized SEEG-guided RF-TC modality that integrates more contacts from multiple different electrodes to create a confluent lesioning field is proposed for a more curative effect in comparison to the current protocol of palliative treatment in which RF-TC selectively disrupts critical hubs in the epileptic network through contiguous contacts within the range of a single electrode. Currently, SEEG-guided RF-TC is indicated for a variety of small, deeply seeded and well-demarcated epileptogenic foci, such as deep heterotopic nodules and hypothalamic hamartoma. The efficacy of treating patients with focal cortical dysplasias in the eloquent cortex and with mesial temporal lobe epilepsy associated with hippocampal sclerosis needs to be further determined. Given the small number of patients reported, randomized controlled trials are necessary to compare the efficacy of SEEG-guided RF-TC with conventional methods in the future. 2020 Annals of Translational Medicine. All rights reserved.