It is important to identify the differentially expressed gene in gastric cancer for elucidating the molecular mechanisms of tumorigenesis of stomach. Here, 38 genes differentially expressed genes between gastric cancer and normal gastric mucosa by in silico approaches. A potassium channel protein KCNE2, identified as a down-regulated gene in gastric cancer, was chosen for further study. We investigated the expression of KCNE2 in gastric cancer tissues and cell lines and examined the effect of KCNE2 on proliferation of gastric cancer. The expression of KCNE2 was markedly down-regulated in gastric cancer tissues and cell lines. Forced overexpression of KCNE2 suppressed the growth of SGC7901 cells and cell cycle progression significantly, which might be related to the down-regulation of Cyclin D1. KCNE2 also inhibited SGC7901 cell growth in soft agar and its tumorigenicity in nude mice. Taken together, our work showed that in silico analysis approaches could be used to identify cancer-related genes effectively. KCNE2, as a novel down-regulated gene in gastric cancer, suppressed cell proliferation and tumorigenesis of stomach.