Objective: To investigate the expressions of Versican and TNF-α in gallbladder carcinoma and their significance. Methods: The expressions of Versican and TNF-α in specimens of 62 gallbladder carcinoma tissues (tumor group), 30 gallbladder tissues with gallstones and chronic inflammation (inflammation group) and 20 normal gallbladder tissues (normal group) were detected by immunohistochemical staining and compared, and the relations of their expressions with clinicopathologic variables and prognosis of gallbladder carcinoma patients were analyzed. Results: Both positive expression rates of Versican and TNF-α presented an ascending order in normal group, inflammation group and tumor group, with statistical difference (all P<0.05); there was a positive correlation between the Versican and TNF-α expression in gallbladder carcinoma tissue (r=0.501, P<0.05). Either Versican or TNF-α expression was significantly related to lymph node metastasis and TNM stage of the patients, and the Versican expression was also related to the degree of differentiation of gallbladder carcinoma (all P<0.05). Survival analysis showed that the survival rate in patients with positive Versican or TNF-α expression was significantly lower than that in their negative counterparts (χ2=5.240, 5.493, both P<0.05), but the survival rate in patients with positive expressions of both Versican and TNF-α had no statistical difference compared with those with the positive expression of either of them alone (both P>0.05). Conclusion: Versican and TNF-α may probably play an important role in the process of occurrence and development of gallbladder carcinoma, and the positive expression of Versican and TNF-α may predict a poor prognosis.