Background: Helicobacter pylori (H pylori) is the most prevalent human infection in half of the world population. Few studies investigated the reasons of infection to H pylori in societies. The current study was designed i to examine the relationship of food insecurity and quality of life with H pylori infection. Methods: In this case- control study, 200 candidates were selected among the people who referred to Shiraz Imam Reza Clinic. They were asked to complete the general questionnaire, food security, and quality of life questionnaires. The H pylori excremental diagnosis test was also taken from them.  Results: The prevalence of H pylori infection was 28%. No relationship was observed between H pylori and age, gender, household size, and body mass index. However, the prevalence of H pylori infection was significantly higher in married individuals and housewives and volunteers with lower educations and those who took digestive medications. In addition, food insecurity (P = 0.04) and low quality of life (P < 0.001) were significantly high in individuals with H pylori infection. However, the possibility of suffering from H pylori infection in individuals who consume digestive medicines was 3.97 times higher than other individuals (95% CI: 2.11-7.40). Furthermore, with reduction of quality of life, the possibility of suffering from H pylori infection increased 1.77 times (95% CI: 1.203-2.591). Conclusion: The data indicated a statistically significant increased risk of H pylori in marital status, occupation, educational level, quality of life, and food insecurity in the affected individuals. The association of food insecurity and quality of life with H pylori infection should be examined in future studies in different populations.