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Background Laboratory studies have shown that gastric epithelial infection cells with Helicobacter pylori (H. pylori) can increase autophagy. Disruption in this process can cause various diseases, including cancer. Objective This study aims to compare the serum level of Autophag -Related Gene 5 (ATG5 ) in individuals with and without H. pylori infection. Methods This case-control pilot study was conducted in 2018 on 44 individuals aged 35-50 years referred to the endoscopy ward of Razi Hospital in Rasht, Iran. Their age, gender, Body Mass Index (BMI), smoking, and symptoms were first recorded in a form. Based on Rapid Urease Test and pathology results, they included in two groups of patient (n=22) and healthy (n=22). Serum ATG5 levels were quantitatively assessed by an ELISA kit (EIAab, USA). Results Most of participants (56.8%) were male, aged over 40 years (77.3%), a BMI < 25 kg/m2 (52.3%) and not smoking cigarettes (70.5%). The mean serum levels of ATG5 in individuals with and without H. pylori infections were 63.5 ± 15.4 and 57.1±18.9, respectively (P>0.05). The mean ATG5 level was higher in women than in men (P= 0.0047). Conclusion Serum level of ATG5 is not significantly different between people with and without H. pylori infection. Further study is recommended using a larger sample size and based on a comparing gastrointestinal lesions. [ABSTRACT FROM AUTHOR]