Background and aim: Bullying is one of the most significant problems that has emerged across the world. It has negative effects on physical, psychological, and social health, especially among adolescents. No previous studies have been conducted in the Jazan region of Saudi Arabia to investigate the association between bullying and health-related quality of life (HRQOL). The study aimed to estimate the prevalence of bullying and its association with HRQOL among adolescents in Jazan.Methods: A cross-sectional study was conducted among 461 adolescents in the Jazan region, Saudi Arabia. They were selected from nine schools by a convenient type of sampling, using snowball technique. HRQOL was tested using the Arabic version of KIDSCREEN-27. Data were collected using a web survey and analyzed by the Statistical Package for Social Sciences (SPSS) version 24 (Armonk, NY: IBM Corp.).Results: The study revealed that 35.3% of all participants were labeled as victims. Victimization was more common among boys (17.78%) than girls (17.57%) (P = 0.001). Most of the victims were bullied verbally (75.6%), and most of them were bullied by friends (57.67%). Regarding sex differences, cyberbullying was more prevalent among girls (18.04%) than among boys (9.82%) (P = 0.01). Bullying was more common in elementary schools (39.5%) than in others. Associations were found between bullying and all aspects of HRQOL that were evaluated (P<0.0001).Conclusions: Bullying prevalence is high among adolescents of the Jazan region and is associated with a poorer quality of life. This requires more attention from families and sectors of education, health, and social services.