Objective: To investigate the efficacy of Anlotinib combined with PD-1 inhibitor in the second-line treatment of elderly patients with advanced lung adenocarcinoma without driver gene mutation and its effect on T lymphocyte subsets. Methods: Elderly patients with advanced lung adenocarcinoma without driver gene mutation were given Pembrolizumab q3w combined with Anlotinib, or Nivolumab q2w combined with Anlotinib. The efficacy was evaluated by solid tumor RECIST 1.1 standard until the patient had disease progression or treatment intolerance. The changes of T lymphocyte subsets in peripheral blood before and after treatment were detected by flow cytometry, and the adverse reactions were monitored. Results: The objective remission rate was 28.1% and the disease control rate was 87.5%; The overall median PFS was 6.2 months. After 2 cycles of treatment, the levels of CD3+, CD4+, CD4+/CD8+cells were significantly higher than those before treatment, and the levels of CD8+ cells were significantly lower than those before treatment (P < 0.01). Conclusion: In the second-line treatment of elderly patients with lung adenocarcinoma without driver gene mutation, Anlotinib combined with PD-1 immunotherapy can improve the short-term efficacy, prolong the progression free survival, help the recovery of immune function and improve the quality of life, and has a good prospect in clinical application.