DNA repair is essential for the successful replication of genetic material and for transcriptional fidelity. Excision repair cross-complementation group 1 (Ercc1) is a structure-specific nucleic acid endonuclease that repairs DNA damage by participating in the nucleotide excision repair and DNA double-strand break repair pathways. The accumulation of various types of molecular and cellular damage over time lead to aging. Defects in Ercc1 are associated with malfunctions in DNA damage repair, Results ing in the accumulation of cellular damage and ultimately inducing aging. This paper summarizes the biological functions of Ercc1 during DNA damage and the phenotypes of Ercc1-deficient mouse models, and discusses the biological effects of Ercc1 in different tissues associated with senescence and age-related degenerative diseases. This review highlights potential intervention targets and provides a theoretical basis for the development of innovative therapeutics, animal models, and drug discovery for senescenceassociated diseases.