Background <p>This study aimed to evaluate the clinical efficacy and safety of nab-paclitaxel in combination with PD-1 inhibitors in elderly patients with advanced squamous cell lung cancer.</p> Methods <p> A retrospective analysis was performed on 40 elderly patients with advanced squamous cell lung cancer treated at the affiliated Zhangjiagang Hospital of Soochow University between March 2020 and July 2024. Patients were assigned to either the chemotherapy group (<i>n</i> = 18), receiving nab-paclitaxel monotherapy, or the combination therapy group (<i>n</i> = 22), receiving nab-paclitaxel plus a PD-1 inhibitor. Treatments were administered every three weeks (per cycle). Short-term efficacy and adverse events were evaluated after every 2–3 cycles, and patients were followed up to assess the incidence of adverse reactions and clinical outcomes, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).</p> Results <p>Compared with the chemotherapy group, patients in the combination therapy group demonstrated improved clinical outcomes, including higher objective response rate(31.8% vs. 22.2%) and disease control rates (86.4% vs. 66.7%), as well as a longer median overall survival time (19 vs. 9 months). In addition, the combination therapy group exhibited significantly higher 6-month (100% vs. 77.8%) and 1-year (72.2% vs. 35.3%) survival rates. The most frequently observed adverse events were leukopenia, anemia, fatigue, nausea and vomiting, myalgia, cough, and interstitial pneumonia, all of which were generally manageable.</p> Conclusion <p>Nab-paclitaxel combined with PD-1 inhibitors demonstrated superior short-term efficacy and an acceptable safety profile compared with chemotherapy alone in elderly patients with advanced squamous cell lung cancer.</p>