Abstract: Lung cancer is the malignant tumor with the highest incidence and lethality globally. In recent years, emerging immunotherapy based on the immune checkpoint inhibitors, programmed cell death protein-1 and its ligand (PD-1/L1), as a representative, has made revolutionary breakthroughs in the field of lung cancer. The indications for this treatment mode have moved from driver-gene-negative advanced or locally advanced lung cancer to adjuvant and neoadjuvant treatment of perioperative lung cancer, and an increasing number of monoclonal antibodies against PD-1 and PD-L1 has been approved for the treatment of lung cancer. However, with the widespread use of immunotherapy, the problem of drug resistance has gradually come to the fore. Only a small proportion of the overall lung cancer population responds to immunotherapy, bringing a new round of challenges to lung cancer treatment. In this paper, the clinical status of immunotherapy resistance in lung caner is reviewed, and cutting-edge advances in knowledge of resistance mechanisms and coping strategies are reviewed, with the aim of providing clinicians with ideas and the basis for formulating individualized, precise treatment plans.