Lung cancer is currently the highest morbidity and mortality malignancy all over the world. In the past, the treatment options available for patients with lung cancer were mainly chemotherapy and tyrosine kinase inhibitors, but after a period of treatment, cancer cells inevitably developed resistance. With the elucidation of the immune escape mechanism of tumor cells recently, immunotherapy, especially immune checkpoint inhibitors, has shown unparalleled advantages in cancer treatment, becoming a new hope for cancer patients after multi-line treatment failure. Immune checkpoint inhibitors usually belong to monoclonal PD-1 or PD-L1 antibody. Pembrolizumab is one of the first immune checkpoint inhibitors approved by the FDA to treat NSCLC and is currently the only immunotherapy drug approved for first-line treatment of NSCLC in immune checkpoint inhibitors. However, there are still some problems to be solved in the clinical application of immune checkpoint inhibitors, such as the lack of effective biomarkers to predict efficacy. Therefore, in this review, we systematically summarize the possible biomarkers that can affect the efficacy of immune checkpoint inhibitors such as PD-L1 expression and tumor mutation burden.