Background: Young people with internet addiction (IA) have been shown to be at risk for having a lower Health-Related Quality Of Life (HRQOL). This study aimed to: identify the risk of internet addiction on health-related quality of life among medical students at Zagazig University during academic year 2022-2023. Subjects and Methods: A cross-sectional comparative study was performed on 280 undergraduate medical students of Faculty of Medicine, Zagazig University. Diagnosis of internet addiction was by using a self administered Arabic semi-structured questionnaire of internet addiction test (IAT). Also, the questionnaire involved socio-demographic data, as well as the World Health Organization Quality of Life Questionnaire-short version (WHOQOL-BREF) questionnaire. Results: About 64% of the studied students were internet addicts and 71% of them were moderate internet addicts. A significant association was revealed between internet addiction and academic performance as 100% of non-internet addict passed the exam and about 3% of internet addicts failed to pass. Also, it was found that internet addict group had significantly lower mean scores on subjective feelings about overall quality of life, all domains of QOL (physical, psychological, social, environmental) and total QOL score compared to non-internet addict group (p<0.001). Also, a highly statistically significant negative correlation was found between internet addiction score with total quality of life score (r=-0.64, P <0.001). Conclusion: More than half of the studied students were internet addict and most of internet addict group suffered from moderate internet addiction. IA was associated with poorer quality of life regarding subjective feelings about overall quality of life and health, all QOL domains' mean scores and global QOL mean score. The negative correlation between internet addiction score with total quality of life score indicating the needs of preventing internet addiction in medical students.