Abstract: Objective To observe the efficacy and safety of gemcitabine combined with xeloda and calcium folinate tablets（GLX） as the first-line regimen for advanced billiary tract cancers（BTCs）. Methods From April 2008 to October 2014，48 patients diagnosed as BTCs by pathologic and imaging examination were treated with GLX as the first-line regimen. Gemcitabine was administrated intravenously at the dose of 1000 mg/m2 for about 30 min on d1 and d8， and Xeloda 1250 mg/m2 and calcium folinate tablets 40-60 mg/m2 twice daily， oral application d1-d14. Regimen was repeated every 3 weeks. The efficacy was evaluated strictly after 2 cycles according to RECIST 1.1 criteria， and quality of life （QoL）was evaluated accoding to karnofsky scores. Side effects was evaluated after 1 cycle according to NCI-CTC 4.0 version criteria. The patients were followed-up for the time to progression （TTP） and overall survival （OS）. Results All patients received 238 cycles totally and mean cylces was 4.9 ranged from 2 to 10. All were eligible for efficacy and toxicity evaluation. There were 1 case of CR, 8 PR and 26 SD. The overall response rate was 18.7% and disease control rate was 72.9%. The medium TTP was 7 months and the medium OS was 13 months. The quality of life（QoL） were improve on 23 cases，stabled on 15 cases and decreased on 10 case with the effective rate of 72.9%. Most common toxicity in grade 3 were leucopenia（6.3%） and hand-foot syndrome （6.3%）. Conclusion GLX as first-line treatment of advanced metastatic BTCs has good effect， and may improve or stabilize the patients QoL with longer TTP and OS. GLX regimen is well tolerated， which is worthy of clinical use and further observation.