Abstract: With the increasing demand of discovering new molecules that specifically modulate certain biological processes in pharmaceutical industry and life sciences, a novel small molecule screening technology for efficient and cost-effective discovery of affinity ligand molecules, the DNA encoded compound library(DEL) screening technology has been developed. DEL is a combinatorial chemical library comprising an unprecedented number of either simple chemicals or those with highly sophisticated structures. Each compound in the library is attached to a unique DNA tag in a covalent manner, allowing the compounds to be pooled and screened against a target protein. The binding hits can subsequently be identified based on the DNA codes through high-throughput sequencing. In recent years, the application of DEL technology in the development of clinical drug candidates has been widely reported. This paper reviews and summarizes the process and progress of DEL technology, especially recent advancements in DEL library construction and affinity screening methods, demonstrates the latest affinity ligand molecules screened and developed by DEL technology. The perspectives of the application of DEL in life sciences including biomedicine and other fields are discussed.