PTP1B (protein tyrosine phosphatase 1B) is a member of the superfamily of PTPs (protein tyrosine phosphatases) and has been implicated in cancer pathogenesis. However, the role of PTP1B in gastric cancer is still unknown. Here, we first detected the PTP1B expression in six gastric cancer cell lines and in the immortalized gastric mucosal epithelial cell line GES-1 by RT-PCR and Western blot. Then, we measured the change of the genome-wide expression profile in MKN28 gastric cancer cells transfected with a plasmid expressing PTP1B-specific small interfering RNA by microarray analysis. Our results showed that PTP1B was overexpressed in gastric cancer cells, and inhibition of PTP1B expression dramatically inhibited gastric cancer cell growth in vitro and in vivo. In addition, microarray analysis revealed that inhibition of PTP1B induced changes in the genome-wide expression profile. These changes may be related to cell growth. Taken together, our data suggested that PTP1B may be a candidate oncogene in gastric cancer.