Gold Nanoparticles (GNPs) are gaining more attention in the field of nanomedicine, particularly in targeted drug delivery and diagnostic probes. More recently, GNPs have been applied in the emerging area of RNA nanotechnology. We studied the effect of 10 nm and 50 nm GNPs on total RNA yield from liver and kidneys of rats. The rats were intraperitoneally injected with 10 nm or 50 nm GNPs for 1 or 5 days and the samples of livers and kidneys were collected 24 h after the last injection. Small portions of tissues were immediately submerged in RNAlater RNA stabilization reagent for in situ stabilization of cellular RNA. Total RNA was extracted using RNAeasy kit and the yield and purity of RNA were measured using a nanodrop spectrophotometer. The total RNA yield was several folds higher from liver as compared to kidneys of rats. Treatment of rats with 10 nm and 50 nm GNPs did not affect the RNA yield from liver whereas the 50 nm GNPs significantly reduced the RNA yield from the kidneys of rats. There was a significant decrease in GAPDH expression in liver and kidney of rats treated with 50 nm GNPs, at day 1 post-dosing.