Telomerase and p53 play critical roles in tumorigenesis and senescence. The mutation of p53 gene and the reactivation of telomerase have been found in most of the human tumors. Aiming telomerase and p53 genes have become important strategies in tumor therapy. We reviewed the aging and tumor phenotype in different status of telomerase and p53 (mTR/p53+/+; mTR/P53/), which indicated that telomere dysfunction could initiate or suppress the tumorigenesis depending on the status of p53. This helps further understanding of the crosstalk between p53 and telomerase in aging and tumorigenesis, and provides a new idea for treating tumor.