Colorectal cancer (CRC) results from multistep and multifactorial processes and is associated with the influences of multiple genes. Recent studies demonstrated that microRNAs (miRNAs) have close relation with the regulation of gene expressions in oncogenesis of CRC. MiRNAs can regulate proteins through their target genes, and these proteins controlled by miRNAs can also in turn modulate the expression of miRNAs, which establishes a complex regulatory network that plays an important role in occurrence and development of tumors. MiR-101 has been found down-regulated in CRC, and regulating the proliferation, invasion and metastasis of CRC cells through multiple target sites and pathways. In this article, the authors address the role of miR-101 in formation and progress of CRC.