Background: Signal transducers and activators of transcription 3(STAT3) is a key transcription factor for many regulatory factors that modulate gene transcription. Dysregulation of STAT3 by constitutive activation plays an important role in the initiation of infl ammation and cellular transformation in numerous cancers. STAT3 activation has been implicated in modulating the activity of downstream mediators such as Bcl-xL and TNF-a. The aim of this study was to investigate the immunohistochemical expressions of STAT3, Bcl-xL and TNF-a proteins in gastric adenoma and adenocarcinoma. Methods: Immunohistochemical staining with monoclonal STAT3, Bcl-xL,, TNF-a antibodies were performed on the paraffi n embedded specimens of 29 gastric adenocarcinomas and 16 gastric adenomas. Results: The expression of STAT3, Bcl-xL and TNF-a was increased in gastric adenoma as compared with gastric adenocarcinoma(P<0.05). The expression of Bcl-xL was higher in intestinal type adenocarcinomas and adenocarcinomas without lymphovascular invasion (p<0.05). The expression of TNF-a was higher in intestinal type, early T stage adenocarcinomas and adenocarcinomas without lymphovascular invasion (P<0.05). Conclusions: STAT3, Bcl-xL and TNF-a may play important roles in the initiation of tumorigenesis of gastric adenocarcinoma.