Aberrant expression of SIRT1, H3K9me3, H3K9Ac and E-cadherin is considered to be associated with tumorigenesis and survival outcomes. In this study, we aim to investigate the expression of SIRT1, H3K9me3, H3K9Ac and E-cadherin and their associations with clinicopathological features in gastric cancer. A total of 105 gastric cancer samples were obtained from patients underwent gastrectomy. Twenty corresponding normal adjacent tissues were simultaneously taken as control. The expression of SIRT1, H3K9me3, H3K9Ac and E-cadherin in these tissues was detected by immunohistochemical and their correlations with clinicopathological features were analyzed. Significant increase of SIRT1 expression was noted in gastric cancer compared with that of normal adjacent tissues (P<0.001). SIRT1 expression was markedly associated with tumor invasion depth (P=0.026), lymph node metastasis (P=0.001), clinical stage (P=0.004) and survival time (P=0.029). No significant difference was identified in the expression of H3K9Ac between gastric and normal tissues. Furthermore, the expression of H3K9Ac was unrelated with gender, age, tumor size, differential degree, invasion depth, lymph node metastasis, clinical stage and survival time (P>0.05). However, H3K9me3 expression was significantly higher in gastric cancer than that in normal tissues (P<0.001), and was remarkably correlated with tumor size (P=0.004), invasion depth (P=0.003), clinical stage (P=0.027) and survival time (P=0.013). In contract, the strong-positive expression of E-cadherin was significantly lower in gastric cancer than that in normal tissues (P<0.05), and its expression was markedly associated with tumor size (P=0.015), differential degree (P=0.031), tumor invasion depth (P<0.001), lymph node metastasis (P<0.001), clinical stage (P< 0.001) and survival time (P< 0.001). Meanwhile, SIRT1 expression was positively correlated with H3K9me3 (r=0.402, P< 0.001), while E-cadherin was negatively associated with SIRT1 (r=-0.285, P=0.003) and H3K9me3 (r=-0.303, P=0.002). Aberrant expression of SIRT1, H3K9me3 and E-cadherin was closely associated with the progression and prognosis in patients with gastric cancer. Also, the expression of such factors were mutually related, based on which may provide an alternative strategy for the clinical diagnosis and treatment by the regulation of their expression in gastric cancer.