Background Gastric cancer (GC) is mostly diagnosed at advanced stage, so prognosis is poor. Therefore, it is necessary to understand the molecular mechanism ofGC development to design new targeted treatment to improve the prognosis ofgastric cancer patients. Aim of the Work To assess the prognostic value ofNEDD-9 and FOXL-1 expression in intestinal type gastric cancer patients, as well as their relationship to clinicopathologic features of the disease and patients outcome. Patients and Methods This is a retrospective study; we included 50 sections from formalin-fixed, paraffin-embedded tissue samples which included intestinal type GC and adjacent non-neoplastic gastric mucosa in the same block that were subjected to immunohistochemistry with anti-NEDD-9 and anti-FOXL-1 antibody. Patients were retrospectively followed up for about 5 years for assessment of tumor progression and survival in relation to marker expression. Results High NEDD-9 and low FOXL-1 expression were found in intestinal type GCmore than adjacent non-neoplastic mucosa (p < 0.001). NEDD-9 high expression and FOXL-1 low expression were associated with presence ofhelicobacter pylori gastritis (p = 0.010, 0.049), high grade (p = 0.007, 0.004), high stage (p <0.001), presence ofdistant metastases (p = 0.029, 0.021), poor DFS (p = 0.003), and OS rates (< 0.001). Conclusion NEDD-9 overexpression and FOXL-1 deficiency in intestinal type GC can help in prediction oftumor prognosis and it can guide the selection ofpatients for future therapies in gastric carcinoma