Objective To explore the effects of miR-335-5p derived from plasma exosomes on immune escape of triple-negative breast cancer (TNBC) via regulating ubiquitin-specific protease 22 (USP22). Methods The plasma of TNBC patients and healthy people was collected, then plasma exosomes were separated, and real time quantitative PCR was used to determine the relative expression of miR-335-5p in exosomes. The interaction between miR-335-5p and USP22 was verified by dual luciferase reporter assay. The expression of miR-335-5p and USP22 in exosomes and MDA-MB-436 cells was regulated. Exosomes or MDA-MB-436 cells were co-cultured with CD8 T lymphocytes and subsequently divided into different groups.The apoptosis of cells in each group was detected by flow cytometry, and the levels of interferon γ (IFN-γ) and tumor necrosis factor α (TNF- α) in each group were detected by ELISA. The effects of USP22 on the stability of programmed death 1 ligand 1(PD-L1) was tested by Western blot analysis. The effects of miR-335-5p and PD-L1 on tumor growth was detected by tumor formation test in nude mice. Results The expression of miR-335-5p in TNBC exosomes was down-regulated. USP22 was confirmed as a target gene of miR-335-5p. In addition, USP22 could inhibit the ubiquitination of PD-L1 protein. Overexpression of miR-335-5p inhibited the immune escape of TNBC. Inhibition of miR-335-5p promoted the immune escape of TNBC, which could be partially saved by USP22 down-regulation. Knockdown of miR-335-5p promoted tumor growth in vivo, while tumor growth was inhibited by the addition of PD-L1 antibody. Conclusion Exosomal miR-335-5p promotes ubiquitination of PD-L1 by USP22 through down-regulating USP22, and inhibits TNBC immune escape mediated by PD-L1.