Cell adhesion molecule 4 (CADM4) is involved in intercellular interactions and is a tumor-suppressor candidate. The role of CADM4 in gallbladder cancer (GBC) has not been reported. Therefore, the clinicopathological significance and prognostic value of CADM4 expression in GBC were evaluated in the present study. Immunohistochemistry (IHC) was performed on 100 GBC tissues to assess CADM4 expression at the protein level. The association between CADM4 expression and the clinicopathological characteristics of GBC was analyzed, and the prognostic significance of CADM4 expression was evaluated. Low CADM4 expression was significantly associated with advanced T category (p = 0.010) and high AJCC stage (p = 0.019). In a survival analysis, low CADM4 expression was associated with shorter overall survival (OS; p = 0.001) and recurrence-free survival (RFS; p = 0.018). In univariate analyses, low CADM4 expression was associated with shorter OS (p = 0.002) and RFS (p = 0.023). In multivariate analyses, low CADM4 expression was an independent prognostic factor of OS (p = 0.013). Low CADM4 expression was associated with tumor invasiveness and poor clinical outcomes in patients with GBC. CADM4 may play an important role in cancer progression and patient survival and can be used as a potential prognostic marker of GBC.