We conducted a phase II study of combination chemotherapy with nedaplatin (NP) with irinotecan (CPT) to determine the effects against unresectable non-small cell lung cancer (NSCLC) and to determine the qualitative and quantitative toxicities of this combination chemotherapy in 70 years or older patients. Thirty-eight patients received 100 mg/m2 NP on day 1 and 60 mg/m2 CPT on days 1 and 8 every four weeks. Twenty-five patients achieved PR, nine SD and three PD, and the overall response rate was 65.8%. Nineteen patients (50%) experienced grade 4 neutropenia. Neutropenic fever occurred in 11 patients (29%) and one of them died. Of other grade 3 non-hematologic toxicities, two patients experienced diarrhea; one interstitial pneumonitis; one liver injury; and one rash. The median survival time was 418 days and the one-year survival rate was 55.3%. In conclusion, NP combined with CPT is an active treatment for elderly patients with NSCLC.