BACKGROUND & OBJECTIVE It was considered that the expression of CD44v6 in gastric cancer was high and Helicobacter pylori (HP) infection was type I carcinogen of gastric cancer. So far, no document has been reported about the relationship between HP infection and CD44v6 expression. This study was designed to investigate the relationship between expression of CD44v6 in gastric cancer and HP infection. METHODS The specimens were divided into three groups:gastric cancer (56 cases), cancer adjacent tissue (56 cases), and gastric mucosa dysplasia (32 cases). The expression of CD44v6 was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis. HP was determined with the rapid urease test and Warthin-Starry staining. Simultaneously, HP cagA antibody was assayed in the serum of 56 patients with gastric cancer. RESULTS HP positive infection group: The positive expression rates of CD44v6 in metastasis cancer (100%, 12/12) and non-metastasis cancer (90.5%, 19/21) were higher than those in paracancer tissue (48.6%, 24/35) and in gastric mucosa dysplasia (23.6%, 6/23). No statistical difference was found between non-metastasis cancer and metastasis cancer (P >0.25). But there were significant differences between gastric mucosa dysplasia and gastric cancer or cancer adjacent tissue (P< 0.005). HP negative infection group: The positive expression rates of CD44v6 in metastasis cancer, non-metastasis cancer, cancer adjacent tissue, and gastric mucosa dysplasia were 66.7%, 51.4%, 35.1%, and 18.1%, respectively; no statistical difference was found between each group. There was a positive correlation between HP infection and CD44v6 expression (P< 0.01). Both CD44v6 expression and HP infection in intestinal type gastric cancer were higher than those in diffuse type gastric cancer (P >0.05). The positive rate of HP cagA antibody in serum was higher than that of HP infection in gastric cancer tissue (P >0.05). CONCLUSION The positive rate of CD44v6 was high in gastric cancer and may serve as a marker for diagnosing gastric cancer. There is obvious correlationship between CD44v6 expression and HP infection.