Background Silent mating type information regulation 2 homolog 1 (SIRT1) and claudin 4 have been implicated in tumorigenesis in many cancers, but their significance in gastric carcinoma (GC) remains unclear. The aim of this study was to assess their possible significance in GC. Materials and methods Immunohistochemistry was performed to examine the expression of SIRT1 and claudin 4 in 68 cases of GC and three adjacent precursor lesions (chronic gastritis, intestinal metaplasia, and dysplasia). Statistical analysis methods were used to evaluate the relationship between SIRT1 and claudin 4 and various clinicopathological parameters. Results SIRT1 and claudin 4 were found highly expressed in GC. The two markers significantly correlated with depth of tumor invasion, distant metastasis, and TNM stage. SIRT1 was positively correlated with advanced tumor grade, whereas claudin 4 was inversely correlated with it. No significant correlation between SIRT1 and claudin 4 was detected. Conclusion The results suggested that both SIRT1 and claudin 4 might be involved in gastric carcinogenesis. The more advanced the TNM GC stage, the higher the expression of SIRT1 and claudin 4. This suggests their possible role in GC progression