Lung cancer is one of the greatest threats to human health, and is initially detected and attacked by the immune system through tumor‐reactive T cells. The aim of this study was to determine the basic characteristics and clinical significance of the peripheral blood T‐cell receptor (TCR) repertoire in patients with advanced lung cancer. To comprehensively profile the TCR repertoire, high‐throughput sequencing was used to identify hypervariable rearrangements of complementarity determining region 3 (CDR3) of the TCR β chain in peripheral blood samples from 64 advanced lung cancer patients and 31 healthy controls. We found that the TCR repertoire differed substantially between lung cancer patients and healthy controls in terms of CDR3 clonotype, diversity, V/J segment usage, and sequence. Specifically, baseline diversity correlated with several clinical characteristics, and high diversity reflected a better immune status. Dynamic detection of the TCR repertoire during anticancer treatment was useful for prognosis. Both increased diversity and high overlap rate between the pre‐ and post‐treatment TCR repertoires indicated clinical benefit. Combination of the diversity and overlap rate was used to categorize patients into immune improved or immune worsened groups and demonstrated enhanced prognostic significance. In conclusion, TCR repertoire analysis served as a useful indicator of disease development and prognosis in advanced lung cancer and may be utilized to direct future immunotherapy. What's new? T cells are essential players in the anti‐cancer immune response. Characterization of the T‐cell receptor (TCR) repertoire is a promising method for assessing tumor activity, directing therapy, and predicting prognosis; however, the importance of the TCR repertoire in lung cancer is unclear. This sequencing analysis found that the peripheral blood TCR repertoire of patients with advanced lung cancer was significantly different from that of healthy individuals. The peripheral blood TCR repertoire correlated with several clinical characteristics and patient immune status. Dynamic TCR repertoire analysis served as a useful indicator of disease development and may be utilized to direct future immunotherapy.