Objective To investigate the nuclear expression of CXC chemokine receptor 4 (CXCR4) in renal cancer, and analyze its relation with renal cancer metastasis and prognosis. Methods A total of 413 patients with renal cancer who were treated in our urologic center from Mar. 2011 to Nov. 2012 were included in the present study. The subcellular expression of CXCR4 was examined by immunofluorescence staining; the correlation between CXCR4 nuclear location and clinical features, prognosis was analyzed. Results We found that 170 of the 413 renal cancer patients were CXCR4 nuclear staining-positive (group A), and the rest 243 cases were CXCR4 nuclear staining-negative (group B); the two groups had matchable baseline data. Compared with group B, group A had significantly higher Robson stage (P <0.01), more frequent cancer embolus (P <0.01), more frequent lymphatic metastasis (P <0.01), and more frequent distant metastasis (P <0.01). The overall survival rate of group A (86.5%, 147/170) was significantly lower than that of group B (97.1%, 236/243; P <0.001). Conclusion Nuclear expression of CXCR4 in renal cancer tissues is associated with higher Robson stage, more frequent cancer embolus, more frequent lymphatic metastasis, more frequent distant metastasis and poor prognosis.