Tiam1-Rac1 signaling plays an important role in the migration, invasion and metastasis of tumor cells. The aim of the present study was to clarify the clinical value of Tiam1 and Rac1 expression in primary gallbladder carcinoma (PGC). Eighty-six PGC tissues were evaluated by immunohistochemistry for Tiam1 and Rac1 expression. The association of Tiam1 and Rac1 expression with clinicopathological characteristics and the univariate survival analysis for the influence of Tiam1 and Rac1 expression on the overall survival were analyzed. Tiam1 and Rac1 immunoreactivities were observed in 72 (83.7%) and 68 (79.1%) of the 86 PGC cases, but not in the non-neoplastic gallbladder tissues, respectively. The tumors with the positive expression of Tiam1 and Rac1 more frequently showed lymph node metastasis (P = 0.01 and 0.008), lymphovascular invasion (P = 0.009 and 0.01) and recurrence (both P = 0.01), respectively. In addition, the tumors with the positive expression of Tiam1 and Rac1 significantly tended to show deeper invasion depth (P = 0.007 and 0.005) and higher TNM stage (both P = 0.005). The Kaplan-Meier survival curves demonstrated that patients with the positive expression of Tiam1 and Rac1 had a significantly shorter survival time than those patients with their negative expression (both P = 0.01). Multivariate analysis revealed that the positive expression of Tiam1 (P = 0.02) and Rac1 (P = 0.02), as well as TNM stage (P = 0.04), to be independently associated with a poor prognosis of patients with PGC. The data from this study suggest for the first time that Tiam1 and Rac1 are frequently expressed in PGC and are associated with decreased survival of the patients. Therefore, Tiam1 and Rac1 expressions may be independent predictors for the poor prognosis in patients with PGC.