Abstract: 1,2,3,4-Tetrahydro-isoquinolines are a significant class of building blocks used in the pharmaceutical and agrochemical industries, and exist widely in a variety of chiral amine drugs. Among them, (S)-1-Phenyl-1,2,3,4-tetrahydro-isoquinoline ((S)-1-Ph-THIQ) is the key precursor for the synthesis of solifenacin, a drug for the treatment of overactive bladder. Imine reductase (IRED)-catalyzed asymmetric reduction of 1-phenyl-3,4-dihydroisoquinoline (1-Ph-DHIQ) is a green and promising route towards chiral 1-Ph-THIQ. However, currently there is only a limited number of reported IREDs that can catalyze the synthesis of chiral 1-Ph-THIQ from 1-Ph-DHIQ, and they may suffer from issues including low activity, poor stereoselectivity, and substrate inhibition. In this study, we first discovered an IRED AdIR1 with considerable properties by screening a panel of IREDs and identified key residues which might affect the activity via homo-modelling and structure comparison. Protein engineering was performed to generate mutant F172Y with elevated catalytic efficiency, which was then characterized in terms of kinetic parameters and thermostability. Finally, preparative synthesis of (S)-1-Ph-THIQ on gram-scale was achieved employing mutant F172Y, demonstrating the considerable applicability of this biocatalytic route in the synthesis of (S)-1-Ph-THIQ.