Objective: To investigate the efficacy and safety of capecitabine maintenance therapy after the first-line capecitabine plus cisplatin (XP regimen) chemotherapy for patients with HER-2 negative advanced gastric cancer. Methods: A total of 82 chemotherapy-naive patients with HER-2 negative advanced gastric cancer were recruited into this study. They were treated with first-line XP regimen, with 21 days as a cycle. The efficacy was evaluated after two cycles of chemotherapy. A maximum six-cycle dosage was given. A total of 59 patients who responded to the therapy were randomly assigned to either group A or B. In group A, 30 patients were given with capecitabine maintenance therapy (1 000 mg/m2, bid, d1–14, q3w) until disease progression or intolerable toxicity. In group B, 29 patients were treated with clinical observation. Results: A total of 416 cycles of the chemotherapy were completed in 59 patients. All patients were evaluated for the therapeutic efficacy. The response rate (RR) and disease control rate (DCR) were 48.78% and 71.95% in the patients. The RR and DCR were 26.67% and 76.67% in group A, and 0.00% and 37.93% in group B, respectively (P<0.05). The median time to progression was longer in group A (7.9 months) than in group B (5.3 months) (P<0.05). The median overall survival time was 14.8 and 13.2 months in group A and B, respectively (P>0.05). The most common adverse events include myelosuppression, nausea/vomiting, diarrhea, peripheral neurotoxicity, mucositis and hand-foot syndrome. No treatment-related death was found. Conclusion: Capecitabine plus cisplatin with subsequent capecitabine maintenance therapy can increase the RR and DCR, prolong the median time to progression in HER-2 negative advanced gastric cancer, with good tolerance and safety.