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Objective: The aim of this study was to observe the efficacy of gemcitabine combined with cisplatin (GP) in advanced non-small cell lung cancer (NSCLC) patients with low expression of ribonucleotide reductase 1 (RRM1) protein using immunohistochemistry. Methods: RRM1 protein expression in tumor tissue was detected by streptavidin-peroxidase (SP) method of immunohistochemistry. GP regimen (gemcitabine 1000-1250 mg d1, d8, cisplatin 75 mg/m2) was given to advanced NSCLC patients with low expression of RRM1 protein. Results: In the total of 40 patients, these patients with RRM1 low expression performing GP chemotherapy had a good response rate, the objective response rate (ORR) was 47.5% (95%CI, 32.02%- 62.98%), and the disease control rate (DCR) was 72.5% (95 % CI, 65.44%-79.56%). ORR is 45.45% (5/11) in the squamous cell carcinoma patients while 48.15% (13/27) in the adenocarcinoma patients. Conclusion: Superior ORR and DCR were found in advanced NSCLC patients with low expression of RRM1 protein expression performing GP regimen.