Abstract: Objective To investigate the efficacy and safety of S1 combined with thalidomide as maintenance treatment for Her-2 negative patients with advanced gastric cancer. Methods The Her-2 negative recurrent metastatic gastric cancer diagnosed in our hospital from January 2014 to December 2017 was collected. The first-line chemotherapy was performed for 4-6 cycles by SOX, XELOX or mFOLFOX6, and 40 patients without disease progression were evaluated after chemotherapy,randomly divided into maintenance group and control group.Maintenance group (20 cases):treatment with S-1 and thalidomide after first-line chemotherapy, to the progress of the disease or serious drug side effects; Control group (20 cases): first line Anti-tumor drugs were discontinued after chemotherapy and only for follow-up observation and symptomatic treatment. The clinical efficacy and adverse reactions of the two groups were analyzed.Results The maintenance group was more objective and effective than the control group, the difference was statistically significant (35.0% vs 0.0%, P<0.05); The disease control rate was increased (75.0% vs 35.0%, P<0.05). The maintenance group mPFS (8.25 months) was longer than the control group (5.5 months), the difference was statistically significant (P<0.05); The mOS of the two groups were 12.8 months and 11.7 months, the difference was not statistically significant (P>0.05). Maintenance group I-II degree leukopenia, fatigue, liver function damage adverse reactions mainly, improved after symptomatic treatment, no toxic side effects stopped treatment and treatment related deaths. Conclusion After the first-line chemotherapy of Her-2 negative advanced gastric cancer, S-1 combined with thalidomide maintenance therapy was effective,well tolerated,safe, effective, and prolonged median progression-free survival