Recent study suggests that newly found small RNAs, such as microRNA, aptamer RNA and so on, have the important roles on the eukaryotic cell function, and several intracellular small RNAs are identified. However, the exact role of small RNA including the protein factors interacted with them has not been clarified. To search the novel interaction between the intracellular small RNA and specific proteins, we prepared the intracellular small RNA-agarose derived from the egg extract of African claw frog, Xenopus laevis. Using this agarose, several Xenopus proteins those might interact with small RNA were obtained. Among them, four proteins strongly interacted with small RNA were analyzed by mass spectroscopy. Result indicated that they could be heat shock protein 90, heat shock protein 70, and ATP synthase alpha and beta subunits, respectively. In the present paper, the biological utility of intracellular small RNA-agarose is discussed.