Abstract: Objective To compare the efficacy and safety of S-1 plus nedaplatin with docetaxel monotherapy in the treatment of secondline chemotherapy for advanced pulmonary squamous cell cancer. Methods In this study， 87 patients with advanced pulmonary squamous carcinoma who had failed firstline platinumbased chemotherapy regimen were enrolled. Forty-three cases received S-1 combined with nedaplatin as observation group and 44 cases received docetaxel monotherapy as control group with every 21 days as one cycle. Response to chemotherapy was assessed in two cycles by RECIST criteria 1.1 and toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria 4.0. The survival and score of quality of life was evaluated at the same time. Results Eighty-seven patients could be evaluated for recent efficacy and adverse reaction. The response rates were 23.3％ and 18.2％ in observation group and control group without significant difference （P＞0.05）. The disease control rate of observation group was 65.1％， higher than 40.9％ of control group with significant difference （P＜0.05）. The median progression free survival （PFS） were 3.6 months（95%CI: 2.44-4.76 months） and 2.9 months（95%CI: 2.54-3.26 months） in observation group and control group with significant difference （P＜0.05）. The score of quality of life in the observation group and control group were both improved, and the differences were not statistically significant（P＞0.05）. The main adverse reaction of the observation group was hematology toxicity and gastrointestinal reaction and in control group was hematology toxicity and oral stomatitis. Adverse reactions could be alleviated by symptomatic treatment. Conclusion S-1 combined with nedaplatin as the second-line treatment of advanced pulmonary squamous cell carcinoma may have a better efficacy compared to docetaxel monotherapy， and its toxicities are tolerable.