The minichromosome maintenance (MCM) family, a core component of DNA replication, is involved in cell cycle process. Abnormal proliferation has been identified as a crucial process in the evolution of colorectal cancer (CRC). However, the roles of the MCM family in CRC remain largely unknown. Here, the expression, prognostic significance and functions of the MCM family in CRC were systematically analyzed through a series of online databases including CCLE, Oncomine, HPA, cBioPortal and cancerSEA. We found all MCM family members were highly expressed in CRC, but only elevation of MCM3 expression was associated with poor prognosis of patients with CRC. Further in vitro and in vivo experiments were performed to examine the role of MCM3 in CRC. Analysis of CCLE database and qRT-PCR assay confirmed that MCM3 was overexpressed in CRC cell lines. Moreover, knockdown of MCM3 significantly suppressed transition of G1 to S phase in CRC cells. Furthermore, down-regulation of MCM3 inhibited CRC cell proliferation, migration, invasion and promoted apoptosis. These findings reveal that MCM3 may function as an oncogene and a potential prognosis biomarker. Thus, the association between abnormal expression of MCM3 and the initiation of CRC deserves further exploration. © 2020 The Author(s).