Cellular senescence is a terminal growth arrest in the G1 phase of the cell cycle, featuring characteristic morphological, biochemical, and epigenetical changes. Cellular senescence results from telomere erosion, DNA damage, hypoxia, or oncogene deregulation, and it is one of main barriers of tumorigenesis. Proto-oncogene c-Myc encodes a transcription factor that can regulate the transcription of many genes, thereby affects different biological processes such as the cell cycle progression, senescence, apoptosis, metabolism, and so on. The c-Myc protein is closely related to cellular senescence, and it has abilities to affect cellular senescence-associated genes (hTERT, p16, p53, Bmi-1 and p27) transcription. The activation of c-Myc not only inhibits replicative senescence, but also can inhibit oncogene-induced senescence. The c-Myc suppresses Ras-induced cellular senescence with help with CDK2. The inactivation of c-Myc induces senescence in untransformed cells(such as human fibroblasts) as well as in many tumor cells. However, similar to ras gene, under certain conditions, c-Myc can induce cell senescence, and contributes to WRN gene-deficient cells senescence.