Ribosomes are conserved macromolecular machines that are responsible for protein synthesis in all cells. While our knowledge of ribosome biogenesis and function has increased significantly in recent years, little is known about how ribosomes are degraded under specific cellular conditions. We recently uncovered that ribosomes are efficiently turned over by selective macroautophagy/autophagy during oncogene-induced senescence (OIS). By profiling the ribosome interactome in human fibroblasts undergoing OIS, we discovered a key role for the de-ubiquitinating enzyme USP10 in guiding this process. Release of USP10 from ribosomes during senescence leads to their enhanced ubiquitination and selective sequestering by autophagy through the SQSTM1/p62 receptor protein. This process is important for sustaining senescence-associated metabolome and secretome alterations.