Novel evidence has confirmed the involvement of dysregulated expression of HOX genes in cancer. HOX genes are a family of 39 transcription factors, divided in four clusters (HOXA to HOXD), that during normal development regulate cell proliferation and specific cell fate. The aim of this study was to investigate whether genes of the HOXC cluster might play a role in renal cancer. The expression of HOXC11 was detected through polymerase chain reaction and immunohistochemical staining, and we demonstrated that HOXC11 was significantly higher in renal cell carcinoma (RCC) compared to normal kidney tissue. We further demonstrated that HOXC11 overexpression in HK-2 human epithelial cell line promoted proliferation, whereas downregulation of HOXC11 endogenous levels in human RCC cells (Caki-2 cells) decreased proliferation. In RCC, expression of HOXC11 and Ki67, a marker of proliferation, correlates strongly with each other (r s = 0.47, p < 0.003). High immunohistochemical expression of HOXC11 was correlated with T stage (p = 0.06), N stage (p = 0.07), disease stage (p = 0.08), and Ki67 expression (p = 0.07), and patients with tumors showing high number of HOXC11-positive cells had shorter overall survival (p = 0.08) and shorter progression-free survival after treatment (p = 0.08) compared with patients with tumors exhibiting low amount of HOXC11-positive cells. Our data suggest that HOXC11 may contribute to RCC carcinogenesis by increasing tumor cell proliferation and imply that HOXC11 may be an important determinant of RCC patient prognosis.