Summary Background This study was designed to determine the recommended dose of a combination of nedaplatin (NED) and nab-paclitaxel (nab-PTX) in chemotherapy-naive patients with advanced squamous non-small-cell lung cancer (NSCLC). Methods Patients received escalating doses of NED on day 1 and nab-PTX on days 1, 8, and 15 every 4 weeks by an intravenous infusion for up to six cycles. Results A dose of 100 mg/m 2 NED and 100 mg/m 2 nab-PTX was determined to be the recommended dose for patients with advanced squamous NSCLC. The study had an overall response rate of 66.7% (95% confidence interval CI: 38.4–88.2) and disease control rate of 93.3% (95% CI: 68.1–99.8). The median progression-free survival time and survival time was 7.0 months (95% CI: 5.9–8.1) and 13.1 months (95% CI: 6.2–20.1), respectively. The most common adverse events were neutropenia (grade 3/4, 33%) and leukopenia (grade 3/4, 27%). Although peripheral neuropathy was observed in 5 patients (grade 1/2), non-hematological toxic effects were relatively mild. Febrile neutropenia, pneumonitis, and treatment-related death were not observed. Conclusions The combination of NED and nab-PTX was a tolerable and effective regimen and its recommended dose was 100 mg/m 2 and 100 mg/m 2 , respectively, in chemotherapy-naive patients with advanced squamous NSCLC (UMIN000010963).