Objective: To investigate the visfatin expression in gastric cancer and its significance as well as its relation with p53. Methods: The expressions of visfatin and mutant p53 in 68 tissue specimens of gastric cancer and their adjacent normal gastric mucosa were examined by immunohistochemical staining, the relations of visfatin expression with the clinicopathologic factors and p53 expression were analyzed, and the influences of visfatin and p53 expression on the survival of the patients were also analyzed. The visfatin expression in different human gastric cell lines and normal gastric mucosal cells was detected by immunofluorescent assay and Western blot analysis respectively, and the alterations in proliferation and colony-forming ability as well as p53 expression were determined in gastric cancer cells after exposure to the visfatin specific inhibitor FK886. Results: The positive expression rate of either visfatin or p53 expression in gastric cancer tissue was significantly higher than that in normal gastric mucosa (both P<0.05), and both expressions were significantly associated with invasion depth, lymph node metastasis and TNM stage (all P<0.05), moreover, there was a significant positive correlation between visfatin and p53 expressions in gastric cancer tissue (r=0.404, P=0.001); the median survival time in patients with visfatin or p53 positive expression was significantly shortened compared with those with their opposite condition (both P<0.05), and the combination analysis of visfatin and p53 showed that the median survival time decreased in a descending order in patients with both negative expression, one of the two positive expression and both positive expression (χ2=15.83, P=0.000). Both results from immunofluorescence and Western blot showed that the visfatin expression levels in all studied gastric cell lines were significantly higher than that in normal gastric mucosal cells with varying degrees (all P<0.05), which was highest in BGC823 cells; after FK866 treatment, the proliferation and colony-forming ability were significantly decreased, and p53 protein expression was significantly up-regulated in BGC823 cells (all P<0.05). Conclusion: The visfatin expression is increased in gastric cancer tissue, which may synergistically interact with p53 to contribute to the progression of gastric cancer.