The heat shock protein 27-kDa (HSP27) has been found overexpressed in several types of human cancer and is associated with treatment resistance and poor prognosis. Recent proteomic studies demonstrate that HSP27 is significantly overexpressed in colorectal cancer (CRC). However, the relationship between HSP27 expression and patient prognosis remains nascent. In the present study, we aimed to investigate the expression of HSP27 and its correlation with clinicopathological parameters in CRC patients. Dysregulated expression of HSP27 was observed in neoplastic lesions, and appears to be involved in disease progression. Immunohistochemical analysis showed that detectable HSP27 expression was found in 145/182 (79.7%) CRC cases. There was a significant correlation between HSP27 expression and TNM stage (P=0.003). Patients with low HSP27 expression had better survival than those with high HSP27 expression. Additionally, multivariate analysis indicated that HSP27 expression is an independent prognostic marker for CRC. These results suggest that elevated expression of HSP27 protein is a frequent event during the progression of CRC. HSP27 might be used as a valuable prognostic marker for patients with CRC.