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Abstract Background The aim of this study was to research whether there was expression of PD-L1 in plasma exosome of NSCLC patients and whether its expression can partly represent PD-L1 expression of corresponding lung tumor tissues. Methods Plasma was collected before and after surgery of NSCLC patients with stage II to stage III. Plasma of NSCLC patients with stage IV was also collected before and after anti-PD-1/PD-L1 therapy. Digital PCR was used to detect PD-L1 and β-actin mRNA expression of plasma exosomes. Expression of PD-L1 in tumor tissues was determined by immunohistochemical staining (22C3). Pearson correlation analysis and wilcoxon rank sum test was performed by SPSS 22.0. Results A total of 126 patients (54 patients with surgery and 72 patients with non-surgery therapy) were participated in this study. Exosomal PD-L1 expression can be detected in all plasma samples. Exosomal expression of PD-L1 calculated by both absolute quantification method and relative quantification method showed a positive correlation with PD-L1 expression of tumor tissues (absolute quantification method: r2=0.289, P = 0.001; relative quantification method: r2=0.547, P = 0.000). However, expression of exosomal PD-L1 calculated by relative quantification calculation showed higher correlation. Exosomal PD-L1 expression significantly decreased after surgery (P  Conclusions Plasma exosomes of NSCLC patients contains substantial expression of PD-L1. Plasma exosomal PD-L1 expression showed high correlation with PD-L1 expression of tumor tissues. Exosomal PD-L1 expression could represent PD-L1 expression of tumor tissues and might be a potential predictive marker for anti-PD-1/PD-L1 therapy. Legal entity responsible for the study Jifeng Feng. Funding The National Natural Science Foundation of China. Disclosure All authors have declared no conflicts of interest.