Self-disgust is a negative appraisal and feeling of the self and one’s own actions that plays an important role in psychological problems. However, evidence about the neural substrate underpinning individual difference in self-disgust and its negative function (i.e., anger rumination) remains inadequate, which would be valuable for understanding the self-mechanism. Here, we employed voxel-based morphometry to explore the neuroanatomical basis of individual difference in self-disgust, measured using the Self-Disgust Scale in 205 healthy volunteers. Whole-brain multiple regression analysis showed that regional gray matter volume (rGMV) in the medial prefrontal cortex (MPFC) was negatively correlated with individual difference in behavioral self-disgust, with sex, age, and total brain volume (TBV) as covariates. Meanwhile, prediction analysis applying four-fold balanced cross-validation with linear regression supported the robustness of the link between rGMV in the MPFC and individual difference in behavioral self-disgust after adjusting for sex, age, and TBV. Furthermore, mediation analysis indicated that rGMV in the MPFC predicted anger rumination (measured by Anger Rumination Scale) through individual difference in behavioral self-disgust after controlling for sex, age, and TBV. The results of this study suggest that the MPFC plays a critical role in individual difference in behavioral self-disgust and its effect on negative affective cognition. Additionally, the present study provides novel perspectives on, and evidence for, the neuroanatomical mechanisms of the negative self and its deleterious effects.