【Abstract】 Objective To investigate the expression and significance of Sirtuin 3 (SIRT3), hypoxia inducible factor-1α (HIF-1α), fibroblast activation protein (FAP) and hepatocyte growth factor (HGF) in gastric cancer tissues in different clinical stages. Methods Cancer tissue samples were collected from 83 patients with gastric cancer, and corresponding adjacent normal tissue samples were selected as control. Immunohistochemical methods were used to detect the expression levels of SIRT3, HIF-1α, FAP and HGF in cancer tissues and normal tissues adjacent to the cancer. The relationship between the expression of SIRT3, HIF-1α, FAP and HGF and the clinical stage of gastric cancer and the correlation in gastric cancer tissue were analyzed. Results The positive expression rate of SIRT3 in gastric cancer tissues was lower than that in adjacent tissues (P＜0.05), but the positive expression rates of HIF-1α and HGF in gastric cancer tissues were higher than those in adjacent tissues (P＜0.05). The positive expression rate of FAP in gastric cancer tissues was 51.81%, which was not expressed in adjacent tissues (P＜0.05). The expressions of SIRT3, HIF-1α, FAP and HGF in gastric cancer tissues were significantly correlated with TNM stage of gastric cancer (P＜0.05). SIRT3 was negatively correlated with the expression of HIF-1α, FAP and HGF in gastric cancer tissues (P＜0.05), HIF-1α was positively correlated with the expression of FAP and HGF (P＜0.05), and FAP was positively correlated with the expression of HGF (P＜0.05). Conclusion The expression levels of SIRT3, HIF-1α, FAP and HGF are correlated with the TNM stage of gastric cancer. They may jointly participate in the occurrence and development of gastric cancer, and the expression of SIRT3 may play a negative role in regulating HIF-1α, FAP and HGF.