Depersonalization-Derealization Disorder (DD) typically manifests as a disruption of body self-awareness. Interoception −defined as the cognitive processing of body signals− has been extensively considered as a key processing for body self-awareness. In consequence, the purpose of this study was to investigate whether there are systematic differences in interoception between a patient with DD and controls that might explain the disembodiment symptoms suffered in this disease. To assess interoception, we utilized a heartbeat detection task and measures of functional connectivity derived from fMRI networks in interoceptive/exteroceptivo/mind-wandering states. Additionally, we evaluated empathic abilities to test the association between interoception and emotional experience. The results showed patient's impaired performance in the heartbeat detection task when compared to controls. Furthermore, regarding functional connectivity, we found a lower global brain connectivity of the patient relative to controls only in the interoceptive state. He also presented a particular pattern of impairments in affective empathy. To our knowledge, this is the first experimental research that assesses the relationship between interoception and DD combining behavioral and neurobiological measures. Our results suggest that altered neural mechanisms and cognitive processes regarding body signaling might be engaged in DD phenomenology. Moreover, our study contributes experimental data to the comprehension of brain-body interactions and the emergence of self-awareness and emotional feelings.