Background/Objectives. Problematic Internet uUse (PIU) is a multifaceted syndrome characterized by excessive or poorly controlled preoccupations, urges, or behaviors regarding Internet use leading to significant impairments in daily life and mental health. Previous research has separately related PIU to loneliness and dissociation, both in adults and adolescents. The aim of the present study is to analyze the mutual relationship between PIU, loneliness, and dissociation in an adolescent sample, in particular evaluating the indirect effect of dissociation on the relationship between loneliness and PIU. Methods. A cross-sectional design was used with 243 Italian high school students (69.1% females), from year 9 to 13 (age: M = 17.1, SD = 1.4 years), who participated in the study from January to June 2020. They completed measures of PIU (Generalized Problematic Internet Use Scale-2), loneliness (UCLA Loneliness Scale), and dissociation (Adolescent Dissociative Experiences Scale). Socio-demographic and contextual variables were also collected (i.e., age, gender, type of school, school year, sport practice, hobby engagement, assessment before/during the COVID-19 pandemic). Data were analyzed using regression, Pearson’s correlation, and mediation analysis. Results. Severe PIU was observed in 8.6% of the sample. None of the socio-demographic and contextual variables had a significant effect on PIU. Positive medium-sized correlations were observed between PIU, loneliness, and dissociation. Mediation analyses showed an indirect effect of loneliness on PIU through dissociation. Conclusions. Feelings of loneliness may significantly exacerbate adolescents’ PIU by increasing their dissociative tendency. Understanding this dynamic is crucial for developing targeted interventions to address both loneliness and dissociation in efforts to mitigate PIU among adolescents.