Background: Gastritis is a superficial and prevalent inflammatory lesion that is considered a public health concernoncecause gastric ulcers and gastric cancer, especially due to Helicobacter pylori infection. Proton pump inhibitors, such as omeprazole, are the most widely used drugs in order to treat this illness. The aim of the study was evaluating the cytogenetic effects of omeprazole in stomach epithelial cells of patients with gastritis in presence and absence of H. pylori, using to this the application of cytogenetic biomarkers and measurements of catalse and superoxide dismutase. Methods: The study included 152 patients from the Gastroenterology Outpatient Clinic of Hospital Getúlio Vargas, Teresina - PI, that reported the continuous and prolonged use of omeprazole in doses of 20, 30 and 40 mg/kg. The participants were divided into groups: (1) patients without gastritis (n = 32); (2) patients without gastritis but with use of OME (n = 24); (3) patients with gastritis (n = 26); (4) patients with gastritis undergoing OME therapy (n = 26); (5) patients with gastritis and H. pylori (n = 22) and (6) patients with gastritis and H. pylori on OME therapy (n = 22). Results: OME induces cytogenetic risks in the epithelium of the stomach due to the formation of micronuclei (group 6> 1,2,3,4,5; group 5> 1,2,3; group 4> 1,2,3); bridges (groups 4 and 6> 1,2,3,5 and group 2> 3,5); buds (groups 2,4,6>, 1,3,5); binucleated cells (group 6> 1,2,3,4,5; group 4> 1,2,3); groups 2 and 3> 1); picnoses (group 6> 1,2,3,4,5), groups 2 and 5> 1,3; group 4> 1,2,3,5); cariorrexis (groups 6 and 4> 1,2,3,5; groups 2,3,5> 1) and karyolysis (groups 2,4, and 6> 1,3,5; groups 3 and 5> 1). These data show that omeprazole induces cytogenetic risks, especially due to infection with H. pylori, thus indicating the clastogenic and/or aneugenic effects, chromosomes changing, gene expression, cytotoxicity and apoptosis. Conclusions: These risks can be attributed to several mechanisms that are still unclear, including oxidative damage, as observed by increases in catalase and superoxide dismutase. Positive correlations between these antioxidant enzymes were obtained with the formation of micronuclei, and negative for picnoses. Thus, the continuous and prolonged use of omeprazole induces genetic instability, which can be monitored, in cytogenetic analyzes, as anticipation for cancer, especially gastric.