Background <p>Healthy lifestyle behaviors (HLBs) are closely associated with adolescents’ health-related quality of life (HRQoL). However, the complex patterns of association between different behaviors and HRQoL, as well as whether these patterns differ by gender, remain unclear.</p> Objective <p>The present study aimed to investigate the patterns of association between specific HLBs and adolescent HRQoL as well as the related gender differences using a network model.</p> Methods <p>Data were drawn from the Database of Youth Health and included 18,663 Chinese adolescents (mean age 14.31 years, <i>SD</i> = 1.84; 49.84% were male). Network analyses and network comparison tests were used to determine the network structure, central nodes, bridge nodes, and gender differences in the adolescent HLBs–HRQoL network.</p> Results <p>The network analyses revealed that sleep duration was the central behavior and the bridge linking HLBs and HRQoL. Network comparison tests showed that gender differences were observed in network structure but not in network strength. The associations between sleep duration and fatigue, as well as between ball sports and sleep duration, were stronger among female adolescents than among male adolescents. Aerobic exercise showed higher centrality for female adolescents, whereas roller sports and pain and discomfort were more central in the male adolescent network.</p> Conclusions <p>The current study provides initial evidence on the structure of association between specific HLBs and HRQoL among Chinese adolescents and the gender differences in network structures. The findings highlight the potential value of these associational patterns for generating hypotheses in future longitudinal and experimental research.</p>