Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) are important co-inhibitory molecules, while regulatory T cells (Tregs) are important suppressor cells. The increase of them in tumor microenvironment is closely related to tumor immune escape and tumor development. PD-L1 plays an important role in the development and function of Tregs. The application of PD-1/PD-L1 blockade also affects the proliferation and function of Tregs, which further participates in the occurrence of drug resistance and hyperprogressive disease. Further understanding of the role and correlation of PD-L1 and Tregs in tumor immunity and immunotherapy can provide new ideas for improving the efficacy of PD-1/PD-L1 blockade.