To determine whether phosphorylated focal adhesion kinase (P-FAK) has prognostic value in colorectal cancer (CRC) and to test whether it has any association with Tensin 4 (TNS4) expression. P-FAK expression was assessed using immunohistochemistry in 462 CRC cases arrayed on a tissue microarray. P-FAK and TNS4 expression were assessed by immunohistochemistry in 40 cases of paired primary colorectal cancer and corresponding hepatic metastases. Nuclear P-FAK expression was observed in 44% of studied cases. Positive nuclear P-FAK expression was associated with shorter disease-specific survival in univariate (p=0.005) and multivariate analysis (p=0.016). P-FAK expression was greater in metastases than the primary tumours (p<0.001) and showed significant association with nuclear TNS4 (p<0.001) in metastases. P-FAK expression is an independent prognostic marker in CRC. The present data suggest that the FAK signalling pathway may interact with TNS4, a known oncogene in CRC.