小分子干扰核糖核酸（英语：small interfering RNA，缩写为siRNA），又译为小干扰核糖核酸，又称短干扰核糖核酸（short interfering RNA）或沉默核糖核酸（silencing RNA），是长度20到25个核苷酸的双股RNA，在生物学上有许多不同的用途。目前已知siRNA主要参与RNA干扰（RNAi）现象，以带有专一性的方式调节基因的表达。此外，也参与一些与RNAi相关的反应途径，例如抗病毒机制或是染色质结构的改变。不过这些复杂机制的反应途径目前尚未明了。 siRNA最早是由英国的戴维·鲍尔库姆（David Baulcombe）团队发现，是植物中的后转录基因沉默（post-transcriptional gene silencing；PTGS）现象的一部分，其研究结果发表于《科学》。2001年，汤玛士·涂许尔（Thomas Tuschl）团队发现合成的siRNA，可诱导哺乳动物体内的RNAi作用，结果发表于《自然》。这项发现引发了利用可控制的RNAi，来进行生物医学研究与药物开发的方法。

Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 base pairs in length. siRNA is essentially a synthetic, man-made, miRNA molecule, and operates within the RNA interference (RNAi) pathway, where it interferes with the expression of specific genes with complementary nucleotide sequences by degrading mRNA after transcription, resulting in no translation. The mechanism by which this occurs is as follows. Once siRNA enters the cell, it binds to a protein complex called Dicer, which dices up siRNA into smaller fragments. One strand of these fragments, in most cases the antisense strand, is loaded into another protein complex called the RNA-induced Silencing Complex (RISC). The strand RISC picks is random, which contributes to the problem of incorrect targeting in siRNA therapy, although in most cases the antisense strand is bound. The strand bound by RISC then links the complex to the messenger RNA (mRNA) by base pairing. The mRNA is cleaved and destroyed so no protein can be synthesized. This leads to a silenced gene, and the disruption of translation.