The purpose of the study was to explore the significance of FGFR4 protein expression in colorectal cancer. Immunohistochemistry showed 46.8% (148/316) tumors positive for FGFR4 and 7.3% (23/316) for adjacent normal specimens. FGFR4 positivity was correlated with shortened disease free survival (DFS) and overall survival (OS). Multivariate analysis revealed that FGFR4 was an independent prognostic factor. FGFR4 silencing markedly reduced the migration and invasion capacity of colorectal cancer cell lines. These results suggest FGFR4 is a potential prognostic and therapeutic marker for colorectal cancer.