In enzymology, a 2,4-dichlorobenzoyl-CoA reductase (EC 1.3.1.63) is an enzyme that catalyzes the chemical reaction

4-chlorobenzoyl-CoA + NADP⁺ + HCl 2,4-dichlorobenzoyl-CoA + NADPH + H⁺

The 3 substrates of this enzyme are 4-chlorobenzoyl-CoA, NADP⁺, and HCl, whereas its 3 products are 2,4-dichlorobenzoyl-CoA (the thioester of 2,4-dichlorobenzoic acid), NADPH, and H⁺.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 4-chlorobenzoyl-CoA:NADP+ oxidoreductase (halogenating). This enzyme participates in degradation of 2,4-dichlorobenzoate.

• Romanov V, Hausinger RP (1996). "NADPH-dependent reductive ortho dehalogenation of 2,4-dichlorobenzoic acid in Corynebacterium sepedonicum KZ-4 and Coryneform bacterium strainNTB-1 via 2,4-dichlorobenzoyl coenzyme A". J. Bacteriol. 178 (9): 2656–61. PMC 177992. PMID 8626335.