Abstract: Objective To observe the curative effect and adverse reactions of DOF regimen combined with thalidomide and DOF regimen alone as the first-line treatment for advanced gastric cancer. Methods A total of 114 patients with advanced gastric cancer were randomly divided into DOF combined with thalidomide group(Combination group) and DOF alone group(Chemotherapy group), 57 cases each, two weeks as a cycle. Recent response rate (RR), median time to progression (mTTP), median survival time(MST) and side effects were analyzed after 4 cycles. Results RR of Combination group and Chemotherapy group were 61.4% and 49.1% (P<0.05 ) ; mTTP were 6.9 and 6.0 months (P<0.05); MST were 10.9 and 10.5 months (P> 0.05); the incidence of nausea and vomiting in Combination group were lower than those in Chemotherapy group(P<0.05), but the peripheral neurotoxicity and constipation in Combination group were higher than those in Chemotherapy group(P<0.05); no statistical difference was observed in other side effects. Conclusion Compared with DOF alone, DOF combined with thalidomide in advanced gastric cancer patients has better RR, mTTP and QOL; at the meantime, the side effects are easier to be tolerated.