Both gemcitabine and UFUR (UFT, tegafur/uracil) are effective agents against chemo-naïve non-small-cell lung cancer (NSCLC). Their effectiveness in patients failing previous chemotherapy is uncertain. Our aim was to evaluate the efficacy of gemcitabine plus UFUR in NSCLC patients who failed previous platinum-based chemotherapy. Forty-five patients were enrolled. The performance status was 1 in 29 patients and 2 in 16 patients. Treatment consisted of gemcitabine 1000 mg/m2 intravenous infusion on days 1 and 8, plus oral UFUR 200 mg/m2/day from days 1 to 14 of every 3 weeks, to a maximum of six cycles, carried out in the outpatient clinic. One hundred and sixty cycles of treatment were given (mean 3.6 cycles per patient). Grade 3 or 4 toxicities included anemia in four patients, leukopenia in three patients, neutropenia in eight patients, thrombocytopenia in four patients, and fatigue in two patients. After two cycles of treatment, seven of 45 patients (15.6%) had a partial response. The median survival was 13.2 months. Survival was better in those with a better performance status (p=0.0006), in those with disease control using the present treatment (p<0.0001), and in those who received Iressa or Tarceva as salvage therapy after failing the present treatment (p=0.0054). In conclusion, salvage chemotherapy using gemcitabine plus UFUR is active, easy to use, and well tolerated in NSCLC patients who have failed previous chemotherapy. Further treatment with EGFR-TKI is also suggested when patients fail the present treatment.