Background: Gastric cancer (GC) still found to be the predominant cancer in Asia.There were very few reports which were focused on population specific biomarker studies with respect to Helicobacter pylori (H. pylori) induced gastric cancer in India. Hence, we aimed to perform this biomarker study involving H. pylori positive and negative healthy serum samples in comparison with H. pylori positive gastric cancer samples. Methods: We have adapted Proteome based approaches to identify serum biomarkers in our Indian population samples. For proteins separation and identification, 2D gel electrophoresis with tandem mass spectrometry approach was performed and thirty differentially regulated protein spots were analyzed. Results: In comparison of H. pylori negative, H. pylori positive healthy serum samples with H. pylori positive gastric cancer serum samples, four proteins including Prohibitin 2, Serum albumin, Apolipoprotein E and Complement factor B were downregulated and eleven proteins including haptoglobin and its isoform, serotransferrin, Immunoglobulins, Apolipoprotein A1, complement factor C3 proteins were upregulated. Conclusion:A panel of proteins, rather than one single protein is a more accurate candidate for a diagnostic marker. In this study, we found, along with other proteins, previously unreported protein- IGKC to be involved in the pathophysiology of gastric cancer.