BACKGROUND/AIMS: Helicobacter pylori infection is linked to the development of gastric cancer. H. pylori-associated gastric inflammation is considered to be the first important step in the histogenesis of such neoplasia. However, studies that compare proteome of gastric mucosa infected with or without H. pylori are lacking. METHODS: We employed proteomics analysis on the endoscopic biopsy specimens of gastric mucosa obtained from two groups (30 cases): healthy subjects without H. pylori infection (15 cases), and gastritis patients with H. pylori infection (15 cases). The pooled proteins obtained from gastric mucosa infected with or without H. pylori were separated by two-dimensional gel electrophoresis and analyzed by a computer-aided program. The altered protein expressions were then identified by mass spectrometry and validated by Western blotting and immunohistochemistry. RESULTS: On mass spectrometry using MALDI TOF(TM) Analyzer, the up-regulation of Keratin 1, ezrin, adenosine triphosphate (ATP) synthase subunit alpha mitochondrial isoform c, Keratin type I cytoskeletal 19, and Keratin type I cytoskeletal 9 were identified; in contrast, 71 kd heat shock cognate protein, ATP synthase subunit alpha mitochondrial precursor, and annexin IV were down-regulated. Among them, membrane cytoskeleton linker ezrin was validated using Western blot and immunohistochemistry. CONCLUSIONS: Expression of ezrin was significantly different between the gastric mucosa with and without H. pylori infection. Therefore, ezrin could be considered a promising potential molecular marker for detecting H. pylori infection in gastric mucosa.