Objective: The aim of the study was to investigate the prospective study if treatment with arsenic trioxide (As2O3) could enhance disease-free survival as adjuvant post-operative chemotherapy for gastric cancer patients and protect bone marrow from the negative effects of chemotherapy. Methods: 84 adults were randomized into two groups. Patients in treat- ment group were treated with As203 and FOLFOX regimen, the other were administered with FOLFOX regimen only. Results: Four patients were withdrawn in treatment group after 3-4 cycles and the reasons were headache and fidgety (n = 2), ar- rhythmia (n = 1) and AST/ALT elevation (n = 1), while 1 patient in control group after 4 cycles for neutropenia. In the treatment group, the median DFS was 28.34 months (95% CI, 25-33 months). While in control group, the median DFS was 24.50 months (95% CI, 20-30 months). This difference was not statistically significant (chi-square: 2.8885; P value: 0.0892). Pa- tients in the same subgroup of node-positive was 29 in the treatment group and 32 in control group, respectively. The median DFS was 27.87 months (95% CI, 25-31 months) in the treatment group and 24.18 months (95% CI, 19-31 months) in the control group with promising statistical significance (HR 1.89; chi-square: 4.78; P value: 0.0287). The most common grades 3-4 toxicity was leucopenia (n = 11) in control group and the difference was significant (chi-square: 3.9768, P value: 0.046) compared with that in treatment group (n = 4). Conclusion: The combination of arsenic trioxide and FOLFOX regimen has a potential advantage of enhancing disease-free survival in patients with gastric cancer in nodal-positive status as post-opera- tive chemotherapy, and protect bone marrow from the negative effects of chemotherapy.