In one-stage dimethyl ether synthesis from syngas, a hybrid catalyst with Cu-based oxide and solid acid is used. An active catalyst for methanol formation with high resistant to carbon dioxide is essential for high efficiency of the process. Besides Cu, Zn and Al, four promising additives were selected and the composition of the seven elements was optimized. Combinatorial tools with high-throughput screening under pressure using 96 well microplates and a data mining technique was used to discover a new catalyst with high tolerance for carbon dioxide. The activity of the catalyst optimized under 30% CO2 (Cu0.459Zn0.184Al0.175Cr0.000B0.181Zr0.001Ga0.000O1.179) was 270g-MeOH/(kg-cat. h) at 1 MPa, 498 K, and H-2/CO/CO2/N-2 = 43/22/30/5, which is much higher than 190g-MeOH/(kg-cat. h) of the catalyst optimized under 5% CO2 (Cu0.472Zn0.t24Al0.165Cr0.000B0.207Zr0.026Ga0.006O1.215). (C) 2003 Elsevier B.V. All rights reserved.