Abstract: Objective To evaluate the efficacy and safety of GEMOX and FOLFOX regimens as first-line chemotherapy for advanced duodenal cancer. Methods From June 2008 to Jan 2016， 30 advanced duodenal cancer patients were analyzed. Only 20 patients received chemotherapy， including 9 patients of GEMOX regimen and 11 patients of FOLFOX regimen as first-line chemotherapy. The efficacy and safety were evaluated by RECIST 1.1 and NCI-CTC 4.0 criteria. Overall survival （OS） and progression-free survival （PFS） were analyzed by Kaplan-Meier method. Results Among patients receiving chemotherapy， CR and PR were not observed. For GEMOX regiem， 6 cases of SD and 3 cases of PD were observed with disease control rate （DCR） of 66.7％. For FOLFOX regiem， 4 cases of SD and 7 cases of PD were observed with DCR of 36.4％. No difference in DCR was observed between different regimes （P＞0.05）. The median OS of GEMOX and FOLFOX regimes were 27.9 months and 15.2 months（P=0.179）. The median PFS of GEMOX regime was 8 months，superior to 4.4 months of FOLFOX regime （P=0.038）. The major treatment-related side effects included leucopenia， neutropenia， nausea， vomiting， fatigue， erythra and etc， mainly in grade1-2. The median OS of patients receiving chemotherapy was 26.9 months，superior to 4.4 months of patients receiving non-chemotherapy （P＜0.001）. Conclusion Chemotherapy was effective in advanced duodenal cancer. Both GEMOX and FOLFOX regimes were effective and well-tolerated in the first-line chemotherapy. GEMOX had a longer PFS in first-line chemotherapy.