Observing models displaying facial expressions of pain elicits neural activity in onlookers' neural structures involved in first-hand experience of pain and in monitoring conflicting information. We investigated whether the purported conflict between the pain and its emotional expression in a model modulates cortical responses elicited by nociceptive laser stimuli in an onlooker. Seeing happy facial expressions, incongruent with the perceptual status attributed to the model, determined a significant reduction in the laser-evoked N2 potential. One of the main sources of this response is the anterior cingulate cortex, an area involved in pain perception, empathy for pain and conflict detection. A pre-activation of the anterior cingulate cortex due to the detection of the emotional conflict may, therefore, be responsible for the reduction of nociceptive-related response in the same brain area. Thus, top-down variables, like the appraisal of the others' emotional status, modulate onlookers' nociceptive-related neural activity.