Abstract: Telomerase and p53 play critical roles in tumorigenesis and senescence. The mutation of p53 gene and the reac-tivation of telomerase have been found in most of the human tumors. Aiming telomerase and p53 genes have become im-portant 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 de-pending 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.