Objective To explore the association between Internet addiction and depression among adolescents, as well as the mediating effects of anxiety and cognitive emotion regulation. Methods An on-site questionnaire survey was conducted among 2 751 students selected from five public junior middle schools in Shanghai from December 2015 to January 2016 by using the Internet Addiction Assessment Scale, Generalized Anxiety Disorder-7, Kutcher Adolescent Depression Scale and Cognitive Emotion Regulation Questionnaire. Results The detection rate of depression was 22.2% (610/2 751), and depression symptoms were more common among students in higher grades and poorer families (P < 0.05). The results of correlation analysis showed that Internet addiction, depression, anxiety, and non-adaptive cognitive emotion regulation strategies were significantly positively correlated, with correlation coefficients ranging from 0.354-0.755 (all P < 0.01). The structural equation model (SEM) indicated that anxiety and maladaptive strategies played parallel mediating roles between Internet addiction and depression. The non-standardized indirect effect values of anxiety and nonadaptive strategies are 0.340 and 0.031, respectively, and the mediating effect of the two accounts for 91.64% and 8.36% of the total indirect effect. Various fit measures indicate that the mediation effect model fits well. (χ2/DF=1.035, GFI=0.975, AGFI=0.939, RMSEA=0.004, TLI=0.999, CFI=0.999, NFI=0.975, IFI=0.999, RFI=0.967). Conclusions Adolescent Internet addiction can predict depression, and it can also play an indirect role through anxiety and non adaptive cognitive emotion regulation strategies.