ZAK protein is a member of the MLK family proteins defined as mediators in the cell cycle. A survey of ZAK gene expression in gastric antral epithelial cells (GAECs) of gastritis and gastric adenocarcinoma patients with Helicobacter pylori genotypes infection can elucidate carcinogenesis of H. pylori genotypes. In a case-control study, ZAK gene expression was evaluated in GAECs biopsy samples of gastritis and gastric adenocarcinoma patients with (n 23, 21) and without H. pylori infection (n 27, 32), respectively. Total RNA was extracted from each gastric antral biopsy samples and cDNA synthesized by using Takara kits. H. pylori virulence genes֝ cDNA were detected by traditional PCR and specific primers. The ZAK gene expression was measured using the relative Real-Time RT PCR. The prevalence of gastric adenocarcinoma was the highest in man and 61-85 aged groups (p < .05). There was no significant correlation between the prevalence of H. pylori infection and patients' demographic groups. This study showed that ZAK gene overexpression gradually increases with increasing age and tumor grade among gastric adenocarcinoma patients. The gastric antral biopsy samples with H. pylori vacA s1m2 genotype infection showed a weak correlation with ZAK gene overexpression (p < .1). ZAK gene expression was higher in GAECs of gastritis cancer than in gastric adenocarcinoma, indicating the protective effect of ZAK against gastric cancer (p < .005). Reducing ZAK gene expression shows the negative correlations with H. pylori infection and gastric adenocarcinoma. © 2021. Springer Science+Business Media, LLC, part of Springer Nature.