AbstractDepressive disorders and internet addiction (IA) are often comorbid. The aims of this study were to examine the network structure of IA in patients with major depressive disorders (MDD) and explore the association between IA and quality of life (QoL) in this population. This was a multicenter, cross-sectional survey. IA and QoL were assessed with the Internet Addiction Test (IAT) and the World Health Organization Quality of Life-brief version, respectively. Node expected influence (EI) was used to identify central symptoms in the network model, while the flow network of QoL was generated to examine its association with IA. A total of 1,657 patients with MDD was included. “Preoccupation with the Internet,” “Job performance or productivity suffer because of the Internet,” and “Neglect chores to spend more time online” were central symptoms. The symptom “Form new relationships with online users” had the strongest direct positive relation with QoL, while “Spend more time online over going out with others” and “Job performance or productivity suffer because of the Internet” had the strongest direct negative relations with QoL. Neglecting work caused by IA correlated with QoL, while making friends online appropriately was related to better QoL among MDD patients. Appropriate interventions targeting the central symptoms may potentially prevent or reduce the risk of IA in MDD patients.