Summary Chemokine receptor, CXCR3, has been increasingly reported to be involved in tumorigenesis and tumor progression, but limited data are available regarding the expression of CXCR3 in gastric cancer (GC). In the present study, the expressions of CXCR3 and its variants were detected in 96 GC and corresponding nontumor gastric tissues by immunohistochemical staining, in 40 freshly frozen GC and nontumor gastric tissues by reverse-transcription polymerase chain reaction and quantitative real-time polymerase chain reaction, and in 10 freshly frozen GC and nontumor gastric tissues by Western blotting. Results revealed that an overexpression of CXCR3 occurs in GC tissues as compared to the nontumor gastric tissues. High level of CXCR3 expression was found to be inversely associated with invasion depth and metastasis ( P = .030 and P = .019, respectively) and directly associated with improved overall survival (log-rank test, P < .001). Furthermore, multivariate analysis showed that high CXCR3 expression acts an independent prognostic factor for GC patients (hazard ratio, 0.379 0.196-0.734; P = .004). The messenger RNA expression of both the CXCR3 variants, CXCR3-A and CXCR3-B, were up-regulated in GC tissues ( P = .006 and P = .002, respectively), although CXCR3-B messenger RNA expression was significantly higher than CXCR3-A, with an average CXCR3-B to CXCR3-A ratio of 1.80. CXCR3-B protein expression was also up-regulated in GC tissues ( P = .023). In conclusion, our study suggested a potential use of CXCR3 overexpression as a prognostic marker for GC and involvement of the up-regulation of CXCR3-B in favorable prognosis of GC patients.