According to the attachment theory, the establishment of emotional bonds with significant figures is an important process in human development throughout life. The quality of the relationships between adolescents and their caregivers in residential care (RC) may act as a protective factor for internal reorganisation and the development of emotional regulation skills. The present study aims to analyse the effect of insecure attachment orientation and the quality of relationships developed with caregivers in RC settings and adolescent emotion regulation. It also aims to assess the mediating role of emotion regulation in the association between attachment and the quality of the relationship with caregivers. The sample consisted of 249 adolescents, aged between 12 and 18 years old, living in RC facilities in Porto (Portugal). The results suggest that perceived insecurity of attachment to significant figures has a negative effect on emotional regulation and on the quality of the relationship with caregivers. We also found a negative mediating effect of the differentiating emotions dimension on the association between attachment and the quality of the relationship with caregivers. It is relevant to highlight the importance of close affective relationships in developing adolescents’ ability to regulate their emotions and particularly the impact of caregivers and their work in residential care.