Background: Gastric cancer (GC) is the most common gastrointestinal cancer in Iran. Helicobacter pylori (H. pylori) accounts as one of the main risk factors for gastric non-cardia cancer (GNCC). It is suggested that high serum selenium level may have a protective role in GNCC. In this cross-sectional study, we determined the serum Se level and the status of H. pylori infection in two populations with GC and functional dyspepsia (FD).Methods: The enrolled patients were 85 (27 women, 58 men) with recent pathologically proven GNCC (adenocarcinoma) and 85 (34 women, 51 men) FD patients. Serum Se was measured by atomic absorption spectrophotometry. H. pylori IgG antibody was detected by quantitative enzyme immunoassay.Results: The mean age in the GNCC and FD patients were 62.85±14.6 and 58.9±14.7 years, respectively (P=0.08). The serum selenium levels were 111.6±27.7 and 129.9±32.1 μg/L (mean±SD) in GNCC and FD patients, respectively (P<0.001). The frequency of H. pylori infection was 49.4% (n=42) and 68.2% (n=58) in GNCC and FD patients (P=0.013). The crude and adjusted odds ratio (OR) between GNCC and the linear effect of serum selenium level were 0.98 and 0.982, respectively (P=0.002). This means that each unit increase in serum selenium level decreases the odds of cancer by 2%.Conclusion: Serum selenium level was significantly lower in GNCC cases. It suggests that lower serum selenium might have some association with the risk of GNCC. H. pylori infection does not play a significant impact on this association.