Objective To investigate the clinical efficacy of camrelizumab combined with nab-PC regimen (albumin-bound paclitaxel + carboplatin) in the treatment of elderly patients with driver gene-negative stage Ⅳ lung squamous cell carcinoma, and its effects on peripheral blood circulating tumor cells (CTC), natural killer cells (NK cells) and granulocytic myeloid-derived suppressor cells (G-MDSC) levels.Methods A total of 106 elderly patients with stage Ⅳ driver gene-negative lung squamous cell carcinoma treated at our hospital between January 2020 and January 2021 were selected as the research objects and divided into two groups according to the random number table method, with 53 cases in each group. Patients in the control group were treated with nab-PC regimen, and those in observation group were treated with camrelizumab plus nab-PC regimen. Both groups were treated in 21-day cycles for 4 cycles. The short-term efficacy of the two groups was evaluated after treatment. Before and after the treatment, the serum tumor markers [squamous cell carcinoma antigen (SCCA), cytokeratin fragment 19 (CYFR21-1), carcinoembryonic antigen (CEA)] of the patients, as well as the levels of CTC, NK cells, and G-MDSC in the peripheral blood were detected. The adverse reactions of the two groups were statistically analyzed during the treatment process. All patients were followed up long-term to compare median progression-free survival (PFS) and overall survival (OS).Results The objective response rate (ORR) of the observation group was 43.40%, significantly higher than that of the control group (24.53%) (P<0.05). The disease control rate (DCR) of the observation group was 84.91%, showing no statistical difference as compared with the control group (71.70%) (P>0.05). After treatment, the levels of serum CYFRA21-1, SCCA and CEA, as well as the levels of peripheral blood CTC and G-MDSC significantly decreased in both groups (P<0.05), with the observation group exhibiting significantly lower levels than the control group (P<0.05). Peripheral blood NK cell levels significantly increased in the observation group after treatment (P<0.05), whereas no significant change was observed in the control group (P>0.05). The post-treatment NK cell level in the observation group were significantly higher than that in the control group (P<0.05). The incidence of anemia, reactive cutaneous capillary endothelial proliferation, and hypothyroidism was significantly higher in the observation group (P<0.05), while no significant differences were observed in other adverse reactions (P>0.05). The median PFS and OS in the observation group were 8.2 months (95% CI: 4.38-9.54) and 15.6 months (95% CI: 10.71-19.71), respectively, significantly longer than those in the control group [6.5 months (95% CI: 3.92-7.49) and 10.58 months (95% CI: 8.84-12.33)] (P<0.05).Conclusion Camrelizumab combined with nab-PC regimen can effectively regulate the levels of peripheral blood CTC, NK cells and G-MDSC in the treatment of elderly driver gene-negative stage Ⅳ lung squamous cell carcinoma, and improve the short-term and long-term efficacy, with relatively overall safety.