Objective To investigate the application of electrocorticogram （ECoG）， electroencephalogram （EEG）， functional magnetic resonance imaging （fMRI）， and stereotactic electroencephalogram （SEEG） in surgical operation of epilepsy patients with negative magnetic resonance imaging （MRI） findings.Methods A total of 246 epilepsy patients who underwent MRI and had negative findings in our hospital from January 2016 to December 2019 were enrolled， and all patients underwent EEG and fMRI to localize the lesion. Surgical resection was performed for the patients with definite localization of the lesion； in addition， ECoG or SEEG was performed again according to the intraoperative situation， and fMRI and EEG were performed after surgery.Results The definite localization rate of lesions was 79.27% （195/246） for EEG and 79.67% （196/246） for fMRI， and there was no significant difference in the definite localization rate of lesions between EEG and fMRI （P>0.05）. There were 50 cases without obvious abnormal discharge by EEG and fMRI examination. The definite localization rate of lesions was 100.00% （26/26） for ECoG and 100.00% （24/24） for SEEG， and there was no significant difference in the definite localization rate of lesions between ECoG and SEEG （P >0.05）.Conclusions EEG， fMRI， SEEG， and ECoG have a good application value in the localization of epileptogenic focus and the guidance of surgical resection in epilepsy patients with negative MRI findings and can achieve accurate localization and effectively guide surgical treatment.