Programmed death ligand 1 (PD-L1) has emerged as an important target in immune checkpoint blo-ckade therapy for cancer. It is expressed in a variety of cells. Its high expression in tumor cells can enhance programmed death 1 (PD-1) inhibitory signals, thus promoting tumor immune escape. In recent years, cancer immunotherapy based on anti-PD-1/PD-L1 antibodies has brought revolutionary changes in cancer treatment. However, cancer immunotherapy produces long-lasting treatment effects only in some people with cancer. For most patients, it has short-term or no effects. Studies have found that the degradation of PD-L1 is critical for treatment response to cancer immunotherapy. Herein, the lysosomal and proteasomal pathways of PD-L1 degradation and the interaction of PD-L1 degradation with cancer immunotherapy are reviewed, aiming to provide new ideas for improving response rate and scope in cancer immunotherapy.