Theoretical prediction of catalytic performance is crucial for the rational design of novel catalysts. In this study, density functional theory (DFT) simulations were carried out to predict the catalytic performance of four ionic liquids (ILs) used as novel non-metal catalysts in the acetylene hydrochlorination reaction, and the obtained catalytic performances were verified via our experimental tests; moreover, both the theoretical and experimental results showed that the catalytic performance of the four IL catalysts followed the order tetraphenylphosphonium bromide (TPPB) > tetraphenylphosphonium chloride (TPPC) > butyltriphenylphosphonium bromide (BuTPPB) ≫ tetraphenylphosphonium tetrafluoroborate (TPPT), and the 15%TPPB/SAC catalyst exhibited efficient catalytic performance when compared with the recently reported non-metal catalysts for the acetylene hydrochlorination reaction. Furthermore, the catalytic mechanisms of the four ILs with different cations and anions were revealed via theoretical Mulliken, partial density of states (PDOS) and electron density difference (EDD) analyses combined with the experimental XPS and XRD characterizations. The results showed that the effects of the anions on the catalytic activity were much significant than those of the cations. A good IL non-metal catalyst for acetylene hydrochlorination would mainly donate electrons to Cl to activate the H-Cl bond, and then, the electrons would be donated back to the IL catalyst in the transition state. This study provides new insights into the design of efficient nonmercuric catalysts for the acetylene hydrochlorination reaction.