In the past decade, systematic evolution of ligands by exponential enrichment (SELEX) technology has been under development, and is a general approach for identification of aptamers or oligonucleotide ligands that bind with high-affinity and specificity to a wide rang of selected molecules on their versatility. The SELEX protocal is a process of synthesis random oligonucleotide sequents library pool, select special aptamers, amplify and iterative in vitro. Combinatorial modify groups libraries offer the convience in the SELEX process, making the screening process fast, easy and high-throughput. Here the current designs and application of modified nucleotides for in SELEX process are reviewed, and expected to further the utility of this method in both practical and theoretical terms.