Objective: To investigate the expressions of mutant p53 (mutp53) and nicotinamide phosphoribosyltransferase (Nampt) in gastric cancer tissue and their influences on prognosis of the patients. Methods: Immunohistochemical staining was performed for detection of the expressions of p53 (immunohistochemical positive stained p53 proteins are mainly mutant type) and Nampt in specimens of gastric cancer tissues along with the adjacent normal gastric mucosa from 68 gastric cancer patients, and the relations of expression statuses of p53 and Nampt with the clinicopathologic factors and prognosis of the patients were analyzed. Results: The positive expression rates of p53 and Nampt in gastric cancer tissue were significantly higher than those in adjacent normal gastric mucosa (both P<0.05). The p53 overexpression was related to tumor size, infiltration depth, lymph node metastasis and TNM stage, while the Nampt overexpression was associated with infiltration depth, lymph node metastasis and TNM stage (all P<0.05). The expression of p53 was positively correlated with that of Nampt in gastric cancer tissue (r=0.982, P<0.05). The median survival time in patients with p53 positive expression was significantly shorter than that in patients with negative p53 expression; moreover, among patients with positive p53 expression, the median survival time in those with concomitant positive Nampt expression was significantly shorter than in those with negative Nampt expression (both P<0.05). Conclusion: Both mutp53 and Nampt expressions are related to the malignant behavior of gastric cancer, further, there is certain relevance between them, and patients with both mutp53 and Nampt overexpressions may face a poor prognosis.