Abstract: The cell cycle is a continuous process of cell division and proliferation, passing down genetic materials from parental generations． Eukaryotic cells complete cell division and proliferation through periodic changes at the protein level, cell cycle disorder is closely related to diseases such as cancer． Protein phosphorylation is a major regulatory modality in the cell cycle, to change molecular structure of proteins, protein interaction with other molecules, and to regulate biological activities/functions of related molecules． Changes in phosphorylation status of cell cycle-related proteins – the so-called “molecular switches”, can finely tune cell cycle progression and cell division． The multisite phosphorylation of cell cycle-related proteins has been extensively studied． A comprehensive review of phosphorylation mechanisms of important proteins in cell cycle regulation is attempted． Novel discoveries and breakthroughs are summarized．