Based on the investigation on nonbonded interactions between solvent and organosulfur molecules, the reaction kinetics of carbonyl sulfide (COS) with chemical solvents in aqueous solutions, and experimental validation, a hybrid solvent (named UDS-2) was designed to simultaneously remove H2S and organosulfurs from sour natural gas at high removal efficiency. The solvent components, which could enhance physical and chemical absorption of methyl mercaptan and COS, were screened using quantum chemistry method coupled with kinetics analysis. The results show that the five-membered sulfur heterocyclic compound (SUL) exhibits significant advantage of physical solubility of methyl mercaptan and COS. Meanwhile, the cyclic amine (CA) with weak steric hindrance effect as well as moderate basicity could enhance chemical removal of COS. UDS-2 solvent was obtained by blending SUL and CA with N-methyldiethanolamine (MDEA) at optimal proportion, and the removal efficiencies for methyl mercaptan, COS, and total organosulfur of UDS-2 were 53.1, 23.9, and 42.4 percentage points higher than those of MDEA. UDS-2 was successfully applied in a natural gas purification plant. Under the operation conditions of absorption pressure of 5.5 MPa, gas flow rate of 8.48 x 10 N m(3)/h, gasliquid ratios of 240 in absorber-I and 471 in absorber-II, the removal efficiencies for methyl mercaptan, COS, and total organosulfur are 77.6%, 74.5% and 75.6%, respectively. The contents of H2S, CO2, and total sulfur in purified gas can be reduced below 0.7 mg/(N m(3)), 0.16 vol % and 43.5 mg/(N m(3)), respectively, which all met the corresponding specification for Chinese first-grade commercial natural gas. Additionally, the low hydrocarbon loss of 1.34 N m(3)/(N m(3) solution) indicates UDS-2 solvent has good selectivity for sulfur compounds over hydrocarbons.