Internet addiction (IA) is common amongst young people, but no data on IA are available in Tibetan middle school students in China. This study compared the prevalence of IA between Tibetan and Han Chinese middle school students, and examined its association with quality of life. The study was conducted in two middle schools in the Tibetan area of Qinghai province and two Han Chinese middle schools in Anhui province, China. Internet addiction, depressive symptoms and quality of life were measured using standardized instruments. Totally, 1,385 students completed the assessments. The overall prevalence of IA was 14.1%; 15.9% in Tibetan students and 12.0% in Han students. After controlling for the covariates, the prevalence of IA was significantly higher in Tibetan students than in Han students (OR = 3.5, p < 0.001). More severe depressive symptoms, religious beliefs and male gender were positively associated with IA, while good family relationship was negatively associated with IA. Internet addiction was also associated with significantly lower QOL in physical, psychological and environmental domains. Internet addiction appears to be common in Chinese middle school students, particularly amongst Tibetan Chinese students. Considering its negative impact on quality of life, appropriate educational programs and preventive measures for IA should be urgently developed.