In recent years, immunotherapy represented by programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has shown remarkable efficacy for lung cancer. However, there are significant differences in the efficacies of PD-1/PD-L1 inhibitors in different patients with lung cancer. Studies have found that exosomal PD-L1 (ePD-L1) can replace the PD-L1 from lung cancer cells to inhibit the activation of T cell and produce immune resistance. At the same time, it can transfer PD-L1 to secondary cells to play the role of immune tolerance and affect the efficacy of immunotherapy. This paper reviews the methods of separation and detection of exosomes and ePD-L1, the immunosuppressive effect of ePD-L1, and the mechanism of ePD-L1 in the progress of lung cancer and immunotherapy.