Objective The ReHo, ALFF, fALFF of resting-state functional magnetic resonance imaging (RS-fMRI) technology were used to study the influencing factors and neural mechanism of cognitive dysfunction in patients with benign epilepsy of childhood with centrotemporal spikes (BECT). Methods Fourteen patients were enrolled (from April 2015 to March 2018) from epilepsy specialist outpatients and Functional Department of Neurosurgery of Tianjin Medical University General Hospital. They underwent the long term VEEG monitoring (one sleep cycle was included at least), the Wechsler Intelligence Scale (China Revised), the head MRI and RS-fMRI examinations. Spike-wave index (SWI), FIQ, VIQ, PIQ scores were calculated. According to full-scale IQ (FIQ), they were divided into two groups: FIQ<90 (scores range from 70 to 89, the average score was 78.3±8.9, 6 cases) and FIQ≥90 (scores range from 90 to 126, the average score was 116.6±12.9, 8 cases). SPSS21.0 statistical software was used to compare the general clinical data and SWI of the two groups, and the correlation between clinical factors and the evaluation results of Wechsler Intelligence Scale was analyzed. The RS-fMRI images were preprocessed and the further data were analysed by two independent samplest-test under the whole brain of regional homogeneity (ReHo), amplitude of low frequency fluctuation (ALFF) and fractional of ALFF (fALFF) methods. The differences of brain activation regions in RS-fMRI between the two groups were observed, and the results of general clinical data, SWI and cognitive function test were compared and analyzed comprehensively. Results The differences of SWI were statistically significant (P<0.05): FIQ<90 group were greater than FIQ≥90 group. The FIQ, VIQ and PIQ of two groups were negatively correlated with SWI (P<0.05). And the FIQ and PIQ were negatively correlated with the total number of seizures (P<0.05). Compared with FIQ≥90 group by two samplet-test based on whole level ReHo, ALFF, fALFF methods, deactivation of brain regions of FIQ<90 group include bilateral precuneus, posterior cingulate and occipital lobe, and enhanced activation of brain regions include left prefrontal cortex, bilateral superior frontal gyrus medial and right precentral gyrus, supplementary motor area, angular gyrus, supramarginal gyrus, middle temporal gyrus, bilateral insular lobe and subcortical gray matter structures. Conclusions Frequent epileptic discharges during slow wave sleep and recurrent clinical episodes were risk factors for cognitive impairment in BECT patients. Repeated clinical seizures and frequent subclinical discharges could cause dysfunction of local brain areas associated with cognition and the default network, resulting in patients with impaired cognitive function.