Lung cancer is the leading cause of cancer-related deaths worldwide,with a complex pathogenesis and significant challenges in clinical treatment.In recent years, the regulatory role of deubiquitinating enzymes in tumorigenesis and progression has garnered increasing attention. As the largest subfamily of deubiquitinating enzymes, ubiquitin-specific proteases (USPs) exert multidimensional regulatory effects on the initiation and progression of lung cancer by precisely modulating the stability of key signaling pathway proteins.This review systematically summarizes the molecular mechanisms by which the USPs family regulates the lung cancer cell cycle progression, proliferation,apoptosis evasion,invasion and metastasis, immune microenvironment remodeling, and therapy resistance. It highlights the molecular networks of key members, such as USP7, USP9X, and USP22, in modulating lung cancer progression through critical signaling pathways, including p53, programmed death ligand 1 (PD-L1), and Wnt/β-catenin. Additionally, the review comprehensively analyzes the latest advances in the development of small-molecule inhibitors targeting USPs and explores their potential applications in precision therapy for lung cancer, aiming to provide a theoretical foundation for novel diagnostic and therapeutic strategies.