Objective: To investigate the efficacy, adverse reactions and quality of life of elderly colorectal cancer patients treated with celecoxib plus Tegafur/gimeracil/oteracil (S-1). Methods: Thirty-one elderly patients diagnosed with advanced colorectal cancer from January 2010 to May 2014 were enrolled. All patients received oral administration of twice daily 40 mg of S-1 and 0.2 g celecoxib for two weeks followed by one-week break, with 3 weeks as a treatment cycle. The treatment response, patients’ quality of life and adverse reactions as well as the changes in D-Dimer, CEA and CA19-9 levels were observed after 6 treatment cycles. Results: In the 31 patients, the response rate was 64.5% and the disease control rate was 87.1%, respectively. Karnofsky score and physical, social and emotion function of the patients were all significantly improved, and the discomfort caused by tumor burden such as fatigue, pain, sleep disorders and anorexia were all significantly relieved after chemotherapy (all P<0.05). The levels of D-Dimer, CEA and CA19-9 were significantly decreased compared with pretreatment values (all P<0.05). The adverse reactions consisted mainly of myelosuppression, loss of appetite, nausea and vomiting, which were all relieved by symptomatic treatments. Conclusion: S-1 plus celecoxib has proven efficacy in treatment of elderly patients with advanced colorectal cancer, and it can also improve the patients’ quality of life and decrease the levels of D-Dimer, CEA and CA19-9, with tolerable toxicity.