The goal of this research was to validate an Italian adaptation of the questionnaire Difficulties in Interpersonal Regulation of Emotions (DIRE) and to investigate its associations with psychopathology. An Italian sample (N = 630) completed the DIRE and the Symptom Checklist-90 (SCL-90). We tested the factorial structure of the DIRE using explorative and confirmatory factorial analyses; we analysed the convergent validity in terms of zero-order correlations with SCL-90 dimensions; and, we conducted multiple regressions to test the predictivity of DIRE factors on specific SCL-90 dimensions. The Italian DIRE replicated the four-factor structure of the original measure, with two interpersonal (Vent and Reassurance-seek) and two intrapersonal (Accept and Avoid) factors. Interpersonal factors resulted correlated with SCL-90 global indexes of psychopathology. Moreover, specific association between DIRE factors and SCL-90 dimensions were found. The Italian DIRE is a reliable and valid measure to evaluate clinically-relevant forms of emotion dysregulation.