Molecularly imprinted polymers (MIPs),as important mimics of antibodies,are chemically synthesized by polymerization in the presence of a target compound.MIPs have found wide applications in important fileds.However,the current molecular imprinting technology suffers from a dilemma;there is often a compromise between the best affinity and the best specificity for MIPs prepared under optimized condi-tions.Herein,we proposed a new strategy called molecular imprinting and cladding (MIC) to solve this issue.The principle is straightforward;after molecular imprinting,a chemically inert cladding thinlayer is generated to precisely cover non-imprinted area.We further proposed a special MIC approach for con-trollably engineering protein binders.The prepared cladded MIPs (cMIPs) exhibited significantly improved affinity and specificity.The general applicability of the proposed strategy and method was ver-ified by engineering of cMIPs for the recognition of a variety of different proteins.The feasibility of cMIPs for real applications was demonstrated by fluorescence imaging of cancer cells against normal cells and immunoassay of C-peptide in human urine.This study opened up a new avenue for controllably engi-neering protein-specific antibody mimics with excellent recognition properties,holding great prospective in important applications such as disease diagnosis and nanomedicine.