In this study, we investigated whether the ERP responses observed during a verbal irony comprehension task might represent the cortical manifestation of the Medial Prefrontal Cortex (MPFC) activity. We performed a tDCS-EEG study in which we analyzed the effects of tDCS polarities (anode, cathode, sham) over the MPFC during a verbal irony task. We presented visual short stories portraying everyday situations followed by written statements in either an ironic or literal condition, whose meaning was referred to in the previous context. We manipulated the valence of the stimuli by presenting positive sentences or negative sentences in the ironic and literal conditions. The results revealed that the participants who received the anodal stimulation showed no differences in the N400 amplitude in response to the literal and the ironic condition. This could suggest that anodal stimulation has modulatory effects on N400 responses during irony comprehension. Our results indicated that the MPFC might be critical in accessing ironic information at the initial stage of irony comprehension. Finally, we found that the ironic compliments were more difficult to understand compared to the literal ones, suggesting that irony comprehension is affected by the valence of the information presented.