Abstract: A series of 1, 2, 4-thiadiazole-3, 5-dione derivatives of trimethoxy gallic acid (4a-4e) were synthesized, and the intermediate products 2, 3 and the target compounds 4a-4e were tested against the proliferation of acute leukemia HL60 by MTT method.The inhibition of cell proliferation, and the synergistic effects of 4b and 4c and the positive control TDZD-8 on the proliferation inhibition of HL60 cells were investigated. The results showed that compounds 2-4 had a certain inhibitory effect on the proliferation of HL60 cells. Among them, compounds 4b and 4c had better inhibitory effects, and their half inhibitory concentrations (IC₅₀) were 10.60 and 6.31 μmol/L, respectively and the IC₅₀ value of TDZD-8 on HL60 cells was 0.30 mmol/L. In addition, 4b and 4c cooperated with TDZD-8 had better proliferation inhibitory effect on the acute leukemia cell line HL60. When the concentrations of 4b and TDZD-8 were 5.0 and 0.34 μmol/L, the synergistic inhibition rate of them was 94.45%, and the collaborative index(CI) value of the synergy index was 0.58; when the concentrations of 5c and TDZD-8 were 5.0 and 0.34 μmol/L, the synergistic inhibition rate was 98.76% and the CI value was 0.31. It could be seen that the new gallic acid 1, 2, 4-thiadiazole-3, 5-dione derivative could potentially act as the drug leader for treating human acute leukemia.