Neuroimaging studies have reported a large network of brain regions involved in altruism. However, these studies are unable to determine if these regions are necessary for altruistic attitudes. Here, we examined the brain-basis of everyday altruistic attitudes ([Self-Report Altruism Scale]; e.g., helping a stranger with car troubles) and potential factors (i.e., alexithymia [Toronto Alexithymia Scale] such as empathic concern [Interpersonal Reactivity Index]) that may moderate this relationship. We carried out whole-brain voxel-based lesion-symptom mapping and region of interest analyses to study a large sample of patients (n = 130) with penetrating traumatic brain injuries. Our results showed that the effect of anterior insula (AI) lesions was moderated by alexithymia, but not empathic concern. The presence of AI lesions, as well as increased alexithymia, were associated with fewer endorsements of resource-costly altruistic attitudes. Empathic concern was positively correlated with endorsements of resource-costly altruistic attitudes. Taken together, our study provides direct evidence that the AI and alexithymia play crucial roles in everyday altruistic attitudes and reinforces the importance of the emotional experience in altruism.