The role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape is a critical area of research in cancer immunotherapy. The PD-L1/PD-1 signaling pathway is a key component of tumor immunosuppression, inhibiting T lymphocyte activation and enhancing tumor cell immune tolerance. Despite the potential of targeting this pathway for cancer treatment, the therapeutic effectiveness remains poor, partly due to the complex and varied molecular mechanisms driving PD-L1/PD-1 expression and activation. This review summarizes the regulation mechanisms of the PD-L1/PD-1 signaling pathway in the tumor microenvironment and their roles in mediating tumor immune escape. Key factors include inflammatory cytokines (IFN-γ, TNF-α, ILs), growth factors (EGF, TGF-β, GM-CSF), hypoxia, and exosomes. These factors can induce PD-L1 expression, promoting tumor immune escape. Additionally, non-coding RNAs (ncRNAs) such as lncRNAs and miRNAs also play significant roles in regulating PD-L1 expression. The review highlights the importance of understanding the tumor microenvironment in developing more effective immunotherapies for cancer patients.The role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape is a critical area of research in cancer immunotherapy. The PD-L1/PD-1 signaling pathway is a key component of tumor immunosuppression, inhibiting T lymphocyte activation and enhancing tumor cell immune tolerance. Despite the potential of targeting this pathway for cancer treatment, the therapeutic effectiveness remains poor, partly due to the complex and varied molecular mechanisms driving PD-L1/PD-1 expression and activation. This review summarizes the regulation mechanisms of the PD-L1/PD-1 signaling pathway in the tumor microenvironment and their roles in mediating tumor immune escape. Key factors include inflammatory cytokines (IFN-γ, TNF-α, ILs), growth factors (EGF, TGF-β, GM-CSF), hypoxia, and exosomes. These factors can induce PD-L1 expression, promoting tumor immune escape. Additionally, non-coding RNAs (ncRNAs) such as lncRNAs and miRNAs also play significant roles in regulating PD-L1 expression. The review highlights the importance of understanding the tumor microenvironment in developing more effective immunotherapies for cancer patients.