CpG island methylation can lead to epigenetic transcription inactivation of the tumor suppressor gene, and in some circumstances it may be the only mechanism of tumor suppressor gene inactivation, which directly results in the occurrence of the tumors. This paper overviews the relations of the CpG island methylation of the tumor suppressor gene such as Syk, and of p15 with colorectal cancer, and also presents related problems and future considerations.