Besides the cap-dependent manner, protein translation can also be initiated in a cap-independent manner by using RNA cis-elements called internal ribosome entry sites (IRESs) to directly recruit ribosomes to mRNA. IRESs were originally found in viruses and later in the eukaryotic cellular mRNAs. Recently, the IRES elements were also found in the circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs). IRESs have been found to play important roles in stress responses, cell survival, cell apoptosis, cell mitosis, tumorigenesis, and tumor progression. Here, we manually curated all experimentally validated IRESs in the published literature and developed a novel nonredundant public database, IRESbase, which contains 554 viral IRESs, 691 human IRESs, and 83 IRESs from other eukaryotic species.