<p>Ubiquitination functions significantly in ageing, contributing to its influences on ageing-related diseases. Being one of the important posttranslational modifications, ubiquitination can make a difference to the stabilization of diverse proteins, which can be reversed by deubiquitinases (DUBs). The mechanisms of ageing such as loss of proteostasis, mitochondrial dysfunction are gradually illustrated and researchers’ attention on ageing-related diseases including cancers is increasing. The association between ubiquitin proteasome system (UPS) and DUBs with cellular ageing and ageing-related diseases are gradually demonstrated while not comprehensively reviewed. In this review, we illustrate the relationship between ubiquitin system with ageing and provide a further introduction of roles of ubiquitin system in ageing-related diseases. To begin with, the fundamentals of ubiquitin system including the ligases, deubiquitinases and processes of ubiquitination/deubiquitination are given. Then, association between ubiquitin and cellular ageing is further discussed. Besides, we concentrate on the detailed roles of deubiquitination in ageing-related diseases, potential therapeutic targets of the ubiquitin system in ageing-related diseases and the relevant clinical trials so that we can have a comprehensive perspective of the clinical potentials of ubiquitin system in ageing-related diseases. In summary, the information concluded here may be assistant for further investigation in ageing-related diseases in the future.</p>