Abstract: The low chrome utilization efficiency and the discharge of large amounts of effluent containing chromium and salt during the traditional chrome tanning process gravely impair the natural environment and human health, and limit the sustainable development of leather industry. In this study, a copolymer with multi-epoxy groups was designed and synthesized by using the free radical copolymerization. The salt-free, chrome-less, high-exhaustion clean chrome tanning application of the prepared copolymer were studied. Based on the interaction between the epoxy group and amino group of collagen under alkaline condition, the copolymer pre-tanning could block the collagen amino group and create pre-crosslinking between collagen fibers, resulting in salt-free pickling in the crust leather. Furthermore, the introduction of polyethylene glycol chain segments could form hydration layer on the fiber surface and inert collagen fibers, prevent the rapid binding of chrome tanning agent on the skin surface during the initial tanning process and promote the uniform penetration of chrome tanning agent inside the skin. Simultaneously, the hydroxyl groups generated by the ring-opening reaction of epoxy groups gave extra binding sites for the following chrome tanning agent, which is beneficial to improve the absorption rate of chrome tanning agent. Results showed that the copolymer pre-tanning could achieve salt-free pickling, and the chrome absorption rate in the chrome-less tanning was improved from 80.5% to 95%. At the same time, the thermal stability, mechanical and sensory properties of resulting leather were significantly improved.