The incidence of colorectal cancer (CRC) has significantly increased in recent decades, which has made this disease an important global health issue. Despite many efforts, there is no useful prognostic or diagnostic biomarker for CRC. Heat shock protein 27 (Hsp27) is one of the most studied members of the Hsp family. It has attracted particular attention in CRC pathogenesis since it is involved in fundamental cell functions for cell survival. Evidence shows that Hsp27 plays important role in CRC progression and metastasis. Hsp27 overexpression has been observed in CRC and is suggested to be associated with CRC’s poor prognosis. In the present review, we focus on the current knowledge of the role of Hsp27 in CRC carcinogenesis and the underlying mechanisms. In addition, we discuss the value of targeting Hsp27 in CRC treatment.