Background and PurposeTranscranial direct current stimulation is an emerging non-invasive neuromodulation technique for focal epilepsy. Because epilepsy is a disease affecting the brain network, our study was aimed to evaluate and predict the treatment outcome of cathodal tDCS by analyzing the ctDCS-induced functional network alterations.MethodsEither the active 5-day, −1.0 mA, 20-min ctDCS or sham ctDCS targeting at the most active interictal epileptiform discharge regions was applied to 27 subjects suffering from focal epilepsy. The functional networks before and after ctDCS were compared employing graph theoretical analysis based on the functional magnetic resonance imaging data. A support vector machine prediction model was built to predict the treatment outcome of ctDCS using the graph theoretical measures as markers.ResultsOur results revealed that the mean clustering coefficient and the global efficiency decreased significantly, as well as the characteristic path length and the mean shortest path length at the stimulation sites in the fMRI functional networks increased significantly after ctDCS only for the patients with response to the active ctDCS. Our prediction model achieved the mean prediction accuracy of 68.3% after the nested cross validation. The mean area under the receiver operating curve was 0.75, which showed good prediction performance.ConclusionThe study demonstrated that the response to ctDCS was related to the topological alterations in the functional networks of epilepsy patients detected by fMRI. The graph theoretical measures were promising for clinical prediction of ctDCS treatment outcome.