A mechanism study of quinine-squaramide catalyzed enantioselective aza-Friedel-Crafts (aza-F-C) reaction is described using density functional theory (DFT). The most favorable pathway is obtained through the discussions of four possible modes of hydrogen bond interactions, in which the nucleophile is activated by the squaramide N-H groups (N-Ha and N-Hb) and the electrophile binds to the protonated amine by hydrogen bonding. Meanwhile, we have also studied the energy barrier of the stereocontrolling transition states that might play a role of stereoselectivity. In addition, noncovalent interaction (NCI) analyses show a series of favorable cooperative noncovalent interactions, including N-H···O and C-H···F hydrogen-bonding, and π···π interactions. The strong interactions and lower barrier were found for TS3R, indicating the preference for the R-configuration adduct, which is in good agreement with the experimental observations.