C4.4A, a metastasis-associated gene, encodes a glycolipid-anchored membrane protein which is overexpressedin several human malignancies. However, there are few data available on C4.4A expression and its relationshipwith progression in gastric cancer. Our study was designed to explore the expression of C4.4A in gastric cancerand to correlate it with clinical outcome. C4.4A expression was studied by quantitative real-time RT-PCR andimmunohistochemistry for assessment of correlations with clinicopathological factors. C4.4A mRNA expressionwas significantly up-regulated in gastric cancer as compared with noncancerous tissue (p<0.05)., being observedin 107 (88.4%) of the 121 gastric cancer cases by immunohistochemistry. We found that the expression of C4.4AmRNA was correlated with size of the tumor, depth of invasion, lymph node metastasis, distant metastasis andTNM stage. Moreover, patients with overexpression of C4.4A has a significantly worse survival (p<0.05). Furthermultivariable analysis indicated that the expression of C4.4A was an independent prognostic indicator for gastriccancer (p<0.05). In conclusion, overexpression of C4.4A correlates with metastatic potential of gastric cancerand C4.4A could be a novel independent prognostic marker for predicting outcome.