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The environmental benefits of utilizing protease as a biocatalyst for wool shrink-resist finishing have been widely recognized. However, the efficacy of individual protease treatment is unsatisfactory due to its incapability towards the outermost cuticle layer of wool fibers that contains hydrophobic fatty acids. In order to weaken the structural integrity of the highly cross-linked scales and promote the enzymatic anti-felting, sodium sulfite and tris (2-carboxyethyl) phosphine hydrochloride (TCEP) were employed in combination with papain, respectively, aiming at obtaining a low shrinkage without unacceptable fiber damages. Based on the synergistic effect of papain and TCEP, the edges of wool scales were slightly destroyed by the reduction of disulfide bonds, accompanied by enzymatic hydrolysis of the keratin component. Through the controlled reduction and hydrolysis of wool scales, satisfactory anti-felting result was achieved without causing severe damage to the fiber interiors. In the presence of 0.25 g/L TCEP and 25 U/mL papain, the area shrinkage of wool fabric decreased to approximately 6 %, with a low strength loss of less than 8 %. Meanwhile, the dyeing behavior of the wool fabric under low-temperature conditions was dramatically improved, leading to decreased energy consumption during production. The present work provides an alternative for eco-friendly finishing of wool fabrics, which can be applied commercially. • A facile strategy was proposed to achieve anti-felting of wool through the combined use of papain and reductant. • Synergistic effect of reductant and papain endows wool with satisfactory anti-felting property and less fiber damage. • A felting shrinkage of less than 6 % was obtained while treating with 25 U/mL of papain and 0.25 g/L of TCEP. • Low-temperature dyeing and less energy consumption were realized after the combined anti-felting finishing of wool fabric. [ABSTRACT FROM AUTHOR]