Chronic granulomatous disease (CGD) represents a group of genetic disorders in which impaired intracellular microbial killing by phagocytes leads to recurrent bacterial and fungal infections and granuloma formation. Granulomatous lesions involved gastrointestinal tract in more than one-third of all CGD patients, with various clinical presentations, and may be life threatening. Corticosteroid therapy may relieve symptoms but increase the risk of infections in such immunocompromised patients. We report here the first successful management, with hydroxychloroquine therapy alone, of a 29-year-old CGD man with severe gastric granulomatous involvement. Hydroxychloroquine appears to be a safe and effective alternative treatment of granulomas in CGD patients.