Minichromosome maintenance (MCM) proteins are key elements that function as a part of the pre-replication complex to initiate DNA replication. Individual MCM proteins also help to regulate transcription, chromatin remodeling and check point responses. Recent studies indicated that MCM expression is abnormal in many tumors (prostate cancer, endometrial cancer, ovarian cancer, liver cancer, lung cancer, glioblastoma, medulloblastoma, etc.), and is associated with the abilities of proliferation, invasion, metastasis in tumor. Clinical studies have shown that MCM proteins are indicators of tumor proliferation and poor prognosis, and are also identified as potential targets for new treatments of cancers. With the discovery of the crystal structure of the MCM protein complex, the underlying mechanism of MCMs, especially those in the tumors, will be further elucidated. It will also help to develop novel small specific molecule inhibitors for targeting MCMs.