Peptic ulcer disease (PUD) is a common illness, affecting a considerable number of people world-wide, and its occurrence can be influenced by environmental and genetic factors. Heat shock proteins (HSPs) function mostly as molecular chaperones, and are induced by various stresses. The A to G transition at position 1267 of the HSPA1B gene was shown to correlate with changes in the level of HSPA mRNA expression. Here, the relation between A1267G polymorphism of the HSPA1B gene and risk of peptic ulcer in the Iranian population was evaluated. One hundred subjects, who underwent gastroscopy, took part in the study. DNA samples extracted from the biopsy tissues were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). After gastroscopy, peptic ulcer was diagnosed for 50 patients; among them the distribution of AA/AB/BB genotypes was 10, 88, and 2%, respectively. As for the other 50 subjects (without peptic ulcer) included in the control group, the AA/AB/BB genotypes were identified as 40, 52 and 8%, respectively. A significant association was found between the HSPA1B genotype and peptic ulcer (6.76 OR; 95% CI, 2.26 - 20.2; p = 0.0006). Thus, the HSPA1B A1267G polymorphism may be a marker of susceptibility to peptic ulcer.