Ionic liquids (ILs) have been proposed as promising solvents for separating C2H2 and C2H4, but screening an industrially attractive IL with high capacity from numerous available ILs remains challenging. In this work, a rapid screening method based on COSMO-RS was developed. We also present an efficient strategy to improve the C2H2 capacity in ILs together with adequate C2H2/C2H4 selectivity with the aid of COSMO-RS. The essence of this strategy is to increase molecular free volume of ILs and simultaneously enhance hydrogen-bond basicity of anions by introducing flexible and highly asymmetric structures, which is validated by a new class of tetraalkylphosphonium ILs featuring long-chain carboxylate anions. At 298.1 K and 1 bar, the solubility of C2H2 in ILs reaches 0.476 mol/mol IL, very high for a physical absorption, with a selectivity of up to 21.4. The separation performance of tetraalkylphosphonium ILs to the mixture of C2H2/C2H4 was also evaluated. (c) 2015 American Institute of Chemical Engineers AIChE J, 61: 2016-2027, 2015