外切酶，或核酸外切酶（英语：exonucleases）可以是单独存在的酶，或是大型酶复合物的一部分。此类酵素能将聚核苷酸链分解成核苷酸。作用方式是将3'或5'端上的磷酸酯键水解。

Exonucleases are enzymes that work by cleaving nucleotides one at a time from the end (exo) of a polynucleotide chain. A hydrolyzing reaction that breaks phosphodiester bonds at either the 3’ or the 5’ end occurs. Its close relative is the endonuclease, which cleaves phosphodiester bonds in the middle (endo) of a polynucleotide chain. Eukaryotes and prokaryotes have three types of exonucleases involved in the normal turnover of mRNA: 5’ to 3’ exonuclease, which is a dependent decapping protein; 3’ to 5’ exonuclease, an independent protein; and poly(A)-specific 3’ to 5’ exonuclease.<ref name">Mukherjee D; et al. (2004). "Analysis of RNA Exonucleolytic Activities in Cellular Extracts". Springer protocols 257: 193–211. doi:10.1385/1-59259-750-5:193. ISBN 1-59259-750-5. PMID 14770007. </ref>