Background: No definite conclusion has yet to be reached for immunotherapy beyond progression(IBP)as the second-line treatment for advanced NSCLC patients with negative driver genes. Therefore, a retrospective study was conducted to evaluate the efficacy of IBP in this population and investigated whether the cycles, best response and progressive mode of first-line immunotherapy could affect the results. Methods: The clinical data of patients with advanced NSCLC whose response was evaluated as progressive disease (PD) after receiving a PD-1/PD-L1 inhibitors as first-line therapy were retrospectively collected and the patients were assigned to the IBP and non-IBP groups. The overall survival (OS), progression-free survival (PFS) were evaluated between the two groups. The survival effects of cycles, best response and progressive mode of first-line immunotherapy were also evaluated. Results: Between January 2019 and January 2022, a total of 121 patients was evaluated as PD after first-line immunotherapy in our institution; 53 (43.8%) patients were included in the IBP group and 68 (56.2%) patients were included in the non-IBP group. The OS and PFS were no significantly different between the two groups. Further analysis revealed the OS was prolonged with the prolongation of first-line medication cycle. The median OS was 15.4m (15.4 vs 10.8 p= 0.029), 16.1m (16.1 vs 10.8 p= 0.021), 16.3m (16.3 vs 10.9 p= 0.015) for patients with ≥4, ≥6, ≥8 cycles in first-line immunotherapy, respectively. The advantages of OS and PFS were also seen in the subgroup of PR (best response) and local progression of first-line immunotherapy. Conclusions: The clinical outcomes of IBP were similar to those of non-IBP in patients with PD after first-line immnuotherapy in advanced NSCLC. But more cycles, PR as best response and local progression in first-line was benefit.