A novel sulfur-tolerant methanol synthesis catalyst MoS2/K2CO3/MgO-SiO2 has been developed and investigated. Using the information from thermodynamic analysis and the reaction path of the syngas system, a preliminary catalyst design for methanol synthesis has been put forth. A series of experiments relating to the effect of alkali and alkaline earth promoters and acid-base supports on the catalytic properties has been tested and discussed. Under the conditions of 533 K, 8.1 MPa, 3000 h(-1), H-2/CO=1.42 and 1350 ppm sulfur content, the conversion of carbon monoxide is 36.1%, methanol selectivity 53.2%, space-time yield of methanol 180.3 g/l(cat) h, which is much higher than what is so far published in the literature.