OBJECTIVE To examine the significance of alteration of p53-regulated apoptosis-induced protein 1 (p53AIP1) expression in gastric carcinogenesis in patients with Helicobacter pylori infection. BACKGROUND H. pylori infection induces gastric mucosal inflammation and DNA damage of epithelial cells, which associate with gastric carcinogenesis. p53AIP1 is expressed after DNA damage and induces apoptosis in human cell lines. METHODS Endoscopic antral and corpus biopsies were obtained from 13 patients with chronic gastritis and 17 with gastric cancer. Expression of p53AIP1 and p53DINP1 mRNA was examined by semiquantitative reverse transcription polymerase chain reaction and mutation of p53 codon-46 was studied by direct sequence analysis. The grade of gastritis was assessed according to the updated Sydney System. Results were compared between patients with gastric cancer and chronic gastritis. RESULTS In the antrum, p53AIP1 mRNA expression was significantly lower in patients with gastric cancer than in those with chronic gastritis (P<0.05). In patients with chronic gastritis, expression of p53AIP1 mRNA was significantly higher in the antrum than in the corpus (P<0.05). In patients with chronic gastritis, antral mucosa with high p53AIP1 expression tended to have severe intestinal metaplasia. No mutation was found at p53 codon-46. CONCLUSIONS In H. pylori-infected gastric mucosa expression of p53AIP1 would be higher when the inflammation is severe or intestinal metaplasia is present. Insufficient expression of p53AIP1 may play a role in gastric carcinogenesis in patients infected with H. pylori infection.