Gastric carcinogenesis is a multiple-stage process. It is believed that a premalignant lesion often precedes or accompanies gastric cancer, although the underlying mechanisms have not been fully elucidated. Here, we revealed that REG Iα was frequently overexpressed not only in gastric cancer tissues, but also in the intestinal metaplastic and atypical dysplasia gland, which are considered precancerous lesions, in 102 patients. To investigate the role of REG Iα in gastric cancer, we employed siRNA-mediated silencing techniques and found that the downregulation of REG Iα significantly inhibited gastric cancer cell proliferation, whereas overexpression of REG Iα promoted proliferation. In addition, REG Iα appeared to have an anti-apoptotic effect in gastric cancer cells, which was associated with the Bad/Bcl-xL/caspase-3 pathway. Furthermore, gastrin was found to activate REG Iα expression and nuclear translocation of β-catenin in gastric cancer cells. Thus, these data suggest that REG Iα, a potential downstream of gastrin, may be involved in gastric carcinogenesis.